The Experts below are selected from a list of 195 Experts worldwide ranked by ideXlab platform
Leslie M Loew - One of the best experts on this subject based on the ideXlab platform.
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a minimal actomyosin based model predicts the dynamics of Filopodia on neuronal dendrites
Molecular Biology of the Cell, 2017Co-Authors: Olena Marchenko, Tatyana Svitkina, Sulagna Das, Igor L Novak, Vladimir Rodionov, Nadia Efimova, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the Filopodia is crucial for synaptogenesis, but the underlying mechanisms are poorly understood. To study Filopodial motility, we collected and analyzed image data on Filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity, and substrate adhesion gives rise to various Filopodial behaviors. We formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility, and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls Dendritic Filopodia dynamics.
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actomyosin dynamics determine the extension and retraction of Filopodia on neuronal dendrites
bioRxiv, 2016Co-Authors: Olena Marchenko, Tatyana Svitkina, Sulagna Das, Igor L Novak, Vladimir Rodionov, Nadia Efimova, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the Filopodia is crucial for synaptogenesis but the underlying mechanisms are poorly understood. To study the Filopodial motility, we collected and analyzed image data on Filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity and substrate adhesion gives rise to various Filopodial behaviors. We have formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls Dendritic Filopodia dynamics.
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Actomyosin Contractility and Actin Polymerization Explain Dynamic Behavior of Dendritic Filopodia
Biophysical Journal, 2013Co-Authors: Olena Marchenko, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled highly dynamic subcellular structures that sprout densely on neuronal dendrites during early brain development. A fraction of Filopodia undergo a transition to Dendritic spines that later mature into synapses - a process crucial for memory formation and learning, and deficient in neurodevelopmental and neurodegenerative diseases. The dynamics of Dendritic Filopodia is also different from that of conventional Filopodia: the former exhibit sustained length fluctuations and cease their dynamic behavior after transition into spines. While actin retrograde flow in Dendritic Filopodia was measured previously, there has been no detailed theoretical description of how the flow is maintained and how length oscillations are sustained in Dendritic Filopodia. We apply mathematical modeling and experimental techniques to dissect and analyze the components of actin-based motility in Dendritic Filopodia, and suggest its role in the subsequent transition into the spine shape. The simulations demonstrate that the movement of actin network influenced by myosin contractility and viscous shear stresses lead to the myosin build up at the base of the filopodium and its consequent retraction. When myosin is inactive, the filopodium grows with the rate of actin polymerization. However, when myosin is active, the processes of polymerization at the tip, and cytoskeletal contraction due to myosin, and resistance to the flow out of the filopod at the base, conspire to produce an actin flow gradient along the Filopodial axis. We have measured average rates of growth and retraction of Filopodia in cultured hippocampal neurons using a custom tip-tracking algorithm. The simulated length fluctuations and actin retrograde flow compare well with the experimental data. We estimate the resistive force at the base of Filopodia necessary to maintain the pattern of growth and shrinking and suggest new experiments to test the proposed mechanism.
Olena Marchenko - One of the best experts on this subject based on the ideXlab platform.
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a minimal actomyosin based model predicts the dynamics of Filopodia on neuronal dendrites
Molecular Biology of the Cell, 2017Co-Authors: Olena Marchenko, Tatyana Svitkina, Sulagna Das, Igor L Novak, Vladimir Rodionov, Nadia Efimova, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the Filopodia is crucial for synaptogenesis, but the underlying mechanisms are poorly understood. To study Filopodial motility, we collected and analyzed image data on Filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity, and substrate adhesion gives rise to various Filopodial behaviors. We formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility, and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls Dendritic Filopodia dynamics.
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actomyosin dynamics determine the extension and retraction of Filopodia on neuronal dendrites
bioRxiv, 2016Co-Authors: Olena Marchenko, Tatyana Svitkina, Sulagna Das, Igor L Novak, Vladimir Rodionov, Nadia Efimova, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the Filopodia is crucial for synaptogenesis but the underlying mechanisms are poorly understood. To study the Filopodial motility, we collected and analyzed image data on Filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity and substrate adhesion gives rise to various Filopodial behaviors. We have formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls Dendritic Filopodia dynamics.
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Actomyosin Contractility and Actin Polymerization Explain Dynamic Behavior of Dendritic Filopodia
Biophysical Journal, 2013Co-Authors: Olena Marchenko, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled highly dynamic subcellular structures that sprout densely on neuronal dendrites during early brain development. A fraction of Filopodia undergo a transition to Dendritic spines that later mature into synapses - a process crucial for memory formation and learning, and deficient in neurodevelopmental and neurodegenerative diseases. The dynamics of Dendritic Filopodia is also different from that of conventional Filopodia: the former exhibit sustained length fluctuations and cease their dynamic behavior after transition into spines. While actin retrograde flow in Dendritic Filopodia was measured previously, there has been no detailed theoretical description of how the flow is maintained and how length oscillations are sustained in Dendritic Filopodia. We apply mathematical modeling and experimental techniques to dissect and analyze the components of actin-based motility in Dendritic Filopodia, and suggest its role in the subsequent transition into the spine shape. The simulations demonstrate that the movement of actin network influenced by myosin contractility and viscous shear stresses lead to the myosin build up at the base of the filopodium and its consequent retraction. When myosin is inactive, the filopodium grows with the rate of actin polymerization. However, when myosin is active, the processes of polymerization at the tip, and cytoskeletal contraction due to myosin, and resistance to the flow out of the filopod at the base, conspire to produce an actin flow gradient along the Filopodial axis. We have measured average rates of growth and retraction of Filopodia in cultured hippocampal neurons using a custom tip-tracking algorithm. The simulated length fluctuations and actin retrograde flow compare well with the experimental data. We estimate the resistive force at the base of Filopodia necessary to maintain the pattern of growth and shrinking and suggest new experiments to test the proposed mechanism.
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modeling actomyosin contractility in motile Dendritic Filopodia resolves spine shape in mature Dendritic spines
Biophysical Journal, 2012Co-Authors: Olena Marchenko, Charles W WolgemuthAbstract:Dendritic spines of hippocampal neurons are receivers of neurotransmission input that occurs during learning and memory.Dendritic spines stabilization and their structural plasticity underlie synaptogenesis and synaptic plasticity. The morphology and motility of Dendritic spines and their precursors, Dendritic Filopodia, depend crucially on the viscoelastic properties of the actin cytoskeleton and its response to myosin II motor contractility. New data on localization of myosin IIB in the Dendritic spine and its precursor Filopodia allows precise modeling of the forces involved in protruding Filopodia, when the actin network as it is contracted by myosin IIB. The periodic growth and shrinking of Filopodia is captured by our model and arises from the competition between contractility and polymerization. The actomyosin contractility and actin polymerization mechanisms are sufficient to reproduce the Filopodia motility observed in vivo hippocampal neuron Dendritic Filopodia. Moving-boundary simulations capture motile Filopodia actin cytoskeleton dynamics and corresponding myosin concentration fluctuations in Filopodia and mature spines. Our results offer new insights into the stabilization of spine morphology and suggest a biomechanical mechanism for the development of mature spine “mushroom” or “stubby” morphologies.
Charles W Wolgemuth - One of the best experts on this subject based on the ideXlab platform.
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evl and mim mtss1 regulate actin cytoskeletal remodeling to promote Dendritic Filopodia in developing neurons
bioRxiv, 2021Co-Authors: Sara S Parker, Charles W Wolgemuth, Adam D Grant, A M Wang, J D Parker, Mackenzie R Roman, Megha Padi, Paul Langlais, Ghassan MouneimneAbstract:SUMMARY Dendritic spines are the postsynaptic compartment of a functional neuronal synapse, and are critical for synaptic connectivity and plasticity. The developmental precursor to Dendritic spines, Dendritic Filopodia, are highly motile protrusions that facilitate synapse formation by sampling the environment for suitable axon partners during development and learning. Despite the significance of the actin cytoskeleton in driving these protrusions, the actin remodeling factors involved in this process are not fully characterized. In this work, we identify a critical function for the Ena/VASP protein EVL in the regulation of Dendritic Filopodia. Amongst the Ena/VASP proteins, EVL is uniquely required for the characteristic morphology and dynamics of Dendritic Filopodia. Using a combination of genetic and optogenetic manipulations, we demonstrate that EVL promotes protrusive motility through membrane-direct actin polymerization at Dendritic Filopodia tips. EVL forms a complex at nascent protrusions and Dendritic Filopodia tips with MIM/MTSS1, an I-BAR protein recently discovered to be important for initiation of Dendritic Filopodia. We propose a model in which EVL cooperates with MIM to elongate and coalesce branched actin filaments, establishing the dynamic lamellipodia-like architecture of Dendritic Filopodia in developing neurons.
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a minimal actomyosin based model predicts the dynamics of Filopodia on neuronal dendrites
Molecular Biology of the Cell, 2017Co-Authors: Olena Marchenko, Tatyana Svitkina, Sulagna Das, Igor L Novak, Vladimir Rodionov, Nadia Efimova, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the Filopodia is crucial for synaptogenesis, but the underlying mechanisms are poorly understood. To study Filopodial motility, we collected and analyzed image data on Filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity, and substrate adhesion gives rise to various Filopodial behaviors. We formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility, and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls Dendritic Filopodia dynamics.
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actomyosin dynamics determine the extension and retraction of Filopodia on neuronal dendrites
bioRxiv, 2016Co-Authors: Olena Marchenko, Tatyana Svitkina, Sulagna Das, Igor L Novak, Vladimir Rodionov, Nadia Efimova, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the Filopodia is crucial for synaptogenesis but the underlying mechanisms are poorly understood. To study the Filopodial motility, we collected and analyzed image data on Filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity and substrate adhesion gives rise to various Filopodial behaviors. We have formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls Dendritic Filopodia dynamics.
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Actomyosin Contractility and Actin Polymerization Explain Dynamic Behavior of Dendritic Filopodia
Biophysical Journal, 2013Co-Authors: Olena Marchenko, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled highly dynamic subcellular structures that sprout densely on neuronal dendrites during early brain development. A fraction of Filopodia undergo a transition to Dendritic spines that later mature into synapses - a process crucial for memory formation and learning, and deficient in neurodevelopmental and neurodegenerative diseases. The dynamics of Dendritic Filopodia is also different from that of conventional Filopodia: the former exhibit sustained length fluctuations and cease their dynamic behavior after transition into spines. While actin retrograde flow in Dendritic Filopodia was measured previously, there has been no detailed theoretical description of how the flow is maintained and how length oscillations are sustained in Dendritic Filopodia. We apply mathematical modeling and experimental techniques to dissect and analyze the components of actin-based motility in Dendritic Filopodia, and suggest its role in the subsequent transition into the spine shape. The simulations demonstrate that the movement of actin network influenced by myosin contractility and viscous shear stresses lead to the myosin build up at the base of the filopodium and its consequent retraction. When myosin is inactive, the filopodium grows with the rate of actin polymerization. However, when myosin is active, the processes of polymerization at the tip, and cytoskeletal contraction due to myosin, and resistance to the flow out of the filopod at the base, conspire to produce an actin flow gradient along the Filopodial axis. We have measured average rates of growth and retraction of Filopodia in cultured hippocampal neurons using a custom tip-tracking algorithm. The simulated length fluctuations and actin retrograde flow compare well with the experimental data. We estimate the resistive force at the base of Filopodia necessary to maintain the pattern of growth and shrinking and suggest new experiments to test the proposed mechanism.
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modeling actomyosin contractility in motile Dendritic Filopodia resolves spine shape in mature Dendritic spines
Biophysical Journal, 2012Co-Authors: Olena Marchenko, Charles W WolgemuthAbstract:Dendritic spines of hippocampal neurons are receivers of neurotransmission input that occurs during learning and memory.Dendritic spines stabilization and their structural plasticity underlie synaptogenesis and synaptic plasticity. The morphology and motility of Dendritic spines and their precursors, Dendritic Filopodia, depend crucially on the viscoelastic properties of the actin cytoskeleton and its response to myosin II motor contractility. New data on localization of myosin IIB in the Dendritic spine and its precursor Filopodia allows precise modeling of the forces involved in protruding Filopodia, when the actin network as it is contracted by myosin IIB. The periodic growth and shrinking of Filopodia is captured by our model and arises from the competition between contractility and polymerization. The actomyosin contractility and actin polymerization mechanisms are sufficient to reproduce the Filopodia motility observed in vivo hippocampal neuron Dendritic Filopodia. Moving-boundary simulations capture motile Filopodia actin cytoskeleton dynamics and corresponding myosin concentration fluctuations in Filopodia and mature spines. Our results offer new insights into the stabilization of spine morphology and suggest a biomechanical mechanism for the development of mature spine “mushroom” or “stubby” morphologies.
Stephen J Smith - One of the best experts on this subject based on the ideXlab platform.
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in vivo imaging of synapse formation on a growing Dendritic arbor
Nature Neuroscience, 2004Co-Authors: Cristopher M Niell, Martin P Meyer, Stephen J SmithAbstract:The form of a neuron's Dendritic arbor determines the set of axons with which it may form synaptic contacts, thus establishing connectivity within neural circuits. However, the dynamic relationship between dendrite growth and synaptogenesis is not well understood. To observe both processes simultaneously, we performed long-term imaging of non-spiny Dendritic arbors expressing a fluorescent postsynaptic marker protein as they arborized within the optic tectum of live zebrafish larvae. Our results indicate that almost all synapses form initially on newly extended Dendritic Filopodia. A fraction of these nascent synapses are maintained, which in turn stabilizes the subset of Filopodia on which they form. Stabilized Filopodia mature into Dendritic branches, and successive iterations of this process result in growth and branching of the arbor. These findings support a 'synaptotropic model' in which synapse formation can direct dendrite arborization.
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Filopodia spines and the generation of synaptic diversity
Neuron, 2000Co-Authors: James D Jontes, Stephen J SmithAbstract:The above studies appear to be generally consistent with the idea that dendrite dynamics and, consequently, patterns of neural connectivity are modulated by electrical activity. Given these facts, it still remains to be determined what this dynamism means to the organism. How large of a role do Filopodia play in synaptogenesis in the developing brain? Is the refinement of topographic maps dependent on active Dendritic Filopodia? How are synapses stabilized? What are the interactions between axonal and Dendritic arbors? What are the cellular and molecular differences responsible for generating a spine versus a filopodium? What are the specific functional and behavioral consequences of these cellular and molecular differences? The fundamental issue here, as elsewhere, is: What goes on in an organism when nobody is watching? Which small scale processes are important for a given large scale process and which are merely happening at the same time in a causally unrelated way? As is beginning to occur (11xJontes, J.D, Buchanan, J, and Smith, S.J. Nat. Neurosci. 2000; 3: 231–237Crossref | PubMed | Scopus (143)See all References, 13xLendvai, B, Stern, E.A, Chen, B, and Svoboda, K. Nature. 2000; 404: 876–881Crossref | PubMed | Scopus (491)See all References), such issues can be addressed by using minimally invasive techniques to watch cellular and molecular dynamics during the normal development and functioning of intact organisms.*To whom correspondence should be addressed (e-mail: sjsmith@leland.stanford.edu).
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evidence for a role of Dendritic Filopodia in synaptogenesis and spine formation
Neuron, 1996Co-Authors: Noam E Ziv, Stephen J SmithAbstract:Abstract Axo-Dendritic synaptogenesis was examined in live hippocampal cell cultures using the fluorescent dyes DiO to label dendrites and FM 4–64 to label functional presynaptic boutons. As the first functional synaptic boutons appeared in these cultures, numerous Filopodia (up to 10 μm long) were observed to extend transiently (mean lifetime 9.5 min) from Dendritic shafts. With progressively increasing numbers of boutons, there were coincident decreases in numbers of transient Filopodia and increases in numbers of stable Dendritic spines. Dendritic Filopodia were observed to initiate physical contacts with nearby axons. This sometimes resulted in Filopodial stabilization and formation of functional presynaptic boutons. These findings suggest that Dendritic Filopodia may actively initiate synaptogenic contacts with nearby (5–10 μm) axons and thereafter evolve into Dendritic spines.
Tatyana Svitkina - One of the best experts on this subject based on the ideXlab platform.
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a minimal actomyosin based model predicts the dynamics of Filopodia on neuronal dendrites
Molecular Biology of the Cell, 2017Co-Authors: Olena Marchenko, Tatyana Svitkina, Sulagna Das, Igor L Novak, Vladimir Rodionov, Nadia Efimova, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the Filopodia is crucial for synaptogenesis, but the underlying mechanisms are poorly understood. To study Filopodial motility, we collected and analyzed image data on Filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity, and substrate adhesion gives rise to various Filopodial behaviors. We formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility, and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls Dendritic Filopodia dynamics.
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Svitkina T. Molecular architecture of synaptic actin cytoskeleton in hippocampal neurons reveals a mechanism of Dendritic spine morphogenesis
2016Co-Authors: Farida Korobova, Tatyana SvitkinaAbstract:Excitatory synapses in the brain play key roles in learning and memory. The formation and functions of postsynaptic mushroom-shaped structures, Dendritic spines, and possibly of presynaptic terminals, rely on actin cytoskeleton remod-eling. However, the cytoskeletal architecture of synapses remains unknown hindering the understanding of synapse morphogenesis. Using platinum replica electron microscopy, we characterized the cytoskeletal organization and molec-ular composition of Dendritic spines, their precursors, Dendritic Filopodia, and presynaptic boutons. A branched actin filament network containing Arp2/3 complex and capping protein was a dominant feature of spine heads and presynaptic boutons. Surprisingly, the spine necks and bases, as well as Dendritic Filopodia, also contained a network, rather than a bundle, of branched and linear actin filaments that was immunopositive for Arp2/3 complex, capping protein, and myosin II, but not fascin. Thus, a tight actin filament bundle is not necessary for structural support of elongated Filopodia-like protrusions. Dynamically, Dendritic Filopodia emerged from densities in the Dendritic shaft, which by electron microscopy contained branched actin network associated with Dendritic microtubules. We propose that Dendritic spine morphogen-esis begins from an actin patch elongating into a Dendritic filopodium, which tip subsequently expands via Arp2/3 complex-dependent nucleation and which length is modulated by myosin II-dependent contractility
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actomyosin dynamics determine the extension and retraction of Filopodia on neuronal dendrites
bioRxiv, 2016Co-Authors: Olena Marchenko, Tatyana Svitkina, Sulagna Das, Igor L Novak, Vladimir Rodionov, Nadia Efimova, Charles W Wolgemuth, Leslie M LoewAbstract:Dendritic Filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the Filopodia is crucial for synaptogenesis but the underlying mechanisms are poorly understood. To study the Filopodial motility, we collected and analyzed image data on Filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity and substrate adhesion gives rise to various Filopodial behaviors. We have formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls Dendritic Filopodia dynamics.
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molecular architecture of synaptic actin cytoskeleton in hippocampal neurons reveals a mechanism of Dendritic spine morphogenesis
Molecular Biology of the Cell, 2010Co-Authors: Farida Korobova, Tatyana SvitkinaAbstract:The high resolution structure of the cytoskeleton in Dendritic spines and their precursors, Dendritic Filopodia, was characterized by platinum replica electron microscopy. The unexpected features o...
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molecular architecture of synaptic actin cytoskeleton in hippocampal neurons reveals a mechanism of Dendritic spine morphogenesis
Molecular Biology of the Cell, 2010Co-Authors: Farida Korobova, Tatyana SvitkinaAbstract:Excitatory synapses in the brain play key roles in learning and memory. The formation and functions of postsynaptic mushroom-shaped structures, Dendritic spines, and possibly of presynaptic terminals, rely on actin cytoskeleton remodeling. However, the cytoskeletal architecture of synapses remains unknown hindering the understanding of synapse morphogenesis. Using platinum replica electron microscopy, we characterized the cytoskeletal organization and molecular composition of Dendritic spines, their precursors, Dendritic Filopodia, and presynaptic boutons. A branched actin filament network containing Arp2/3 complex and capping protein was a dominant feature of spine heads and presynaptic boutons. Surprisingly, the spine necks and bases, as well as Dendritic Filopodia, also contained a network, rather than a bundle, of branched and linear actin filaments that was immunopositive for Arp2/3 complex, capping protein, and myosin II, but not fascin. Thus, a tight actin filament bundle is not necessary for structural support of elongated Filopodia-like protrusions. Dynamically, Dendritic Filopodia emerged from densities in the Dendritic shaft, which by electron microscopy contained branched actin network associated with Dendritic microtubules. We propose that Dendritic spine morphogenesis begins from an actin patch elongating into a Dendritic filopodium, which tip subsequently expands via Arp2/3 complex-dependent nucleation and which length is modulated by myosin II-dependent contractility.