The Experts below are selected from a list of 321 Experts worldwide ranked by ideXlab platform
Jennifer L. Sallee - One of the best experts on this subject based on the ideXlab platform.
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mutations in drosophila crinkled myosin viia disrupt denticle morphogenesis
Developmental Biology, 2021Co-Authors: Janice M. Crawford, Jennifer L. Sallee, Vinay Singh, Daniel P. KiehartAbstract:Actin filament crosslinking, bundling and Molecular Motor Proteins are necessary for the assembly of epithelial projections such as microvilli, stereocilia, hairs, and bristles. Mutations in such Proteins cause defects in the shape, structure, and function of these actin - based protrusions. One protein necessary for stereocilia formation, Myosin VIIA, is an actin - based Motor protein conserved throughout phylogeny. In Drosophila melanogaster, severe mutations in the MyoVIIA homolog crinkled (ck) are "semi - lethal" with only a very small percentage of flies surviving to adulthood. Such survivors show morphological defects related to actin bundling in hairs and bristles. To better understand ck/MyoVIIA's function in bundled - actin structures, we used dominant female sterile approaches to analyze the loss of maternal and zygotic (M/Z) ck/MyoVIIA in the morphogenesis of denticles, small actin - based projections on the ventral epidermis of Drosophila embryos. M/Z ck mutants displayed severe defects in denticle morphology - actin filaments initiated in the correct location, but failed to elongate and bundle to form normal projections. Using deletion mutant constructs, we demonstrated that both of the C - terminal MyTH4 and FERM domains are necessary for proper denticle formation. Furthermore, we show that ck/MyoVIIA interacts genetically with dusky - like (dyl), a member of the ZPD family of Proteins that links the extracellular matrix to the plasma membrane, and when mutated also disrupts normal denticle formation. Loss of either protein alone does not alter the localization of the other; however, loss of the two Proteins together dramatically enhances the defects in denticle shape observed when either protein alone was absent. Our data indicate that ck/MyoVIIA plays a key role in the formation and/or organization of actin filament bundles, which drive proper shape of cellular projections.
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Mutations in Drosophila crinkled/Myosin VIIA disrupt denticle morphogenesis.
Developmental biology, 2020Co-Authors: Jennifer L. Sallee, Janice M. Crawford, Vinay Singh, Daniel P. KiehartAbstract:Actin filament crosslinking, bundling and Molecular Motor Proteins are necessary for the assembly of epithelial projections such as microvilli, stereocilia, hairs, and bristles. Mutations in such Proteins cause defects in the shape, structure, and function of these actin - based protrusions. One protein necessary for stereocilia formation, Myosin VIIA, is an actin - based Motor protein conserved throughout phylogeny. In Drosophila melanogaster, severe mutations in the MyoVIIA homolog crinkled (ck) are "semi - lethal" with only a very small percentage of flies surviving to adulthood. Such survivors show morphological defects related to actin bundling in hairs and bristles. To better understand ck/MyoVIIA's function in bundled - actin structures, we used dominant female sterile approaches to analyze the loss of maternal and zygotic (M/Z) ck/MyoVIIA in the morphogenesis of denticles, small actin - based projections on the ventral epidermis of Drosophila embryos. M/Z ck mutants displayed severe defects in denticle morphology - actin filaments initiated in the correct location, but failed to elongate and bundle to form normal projections. Using deletion mutant constructs, we demonstrated that both of the C - terminal MyTH4 and FERM domains are necessary for proper denticle formation. Furthermore, we show that ck/MyoVIIA interacts genetically with dusky - like (dyl), a member of the ZPD family of Proteins that links the extracellular matrix to the plasma membrane, and when mutated also disrupts normal denticle formation. Loss of either protein alone does not alter the localization of the other; however, loss of the two Proteins together dramatically enhances the defects in denticle shape observed when either protein alone was absent. Our data indicate that ck/MyoVIIA plays a key role in the formation and/or organization of actin filament bundles, which drive proper shape of cellular projections.
Daniel P. Kiehart - One of the best experts on this subject based on the ideXlab platform.
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mutations in drosophila crinkled myosin viia disrupt denticle morphogenesis
Developmental Biology, 2021Co-Authors: Janice M. Crawford, Jennifer L. Sallee, Vinay Singh, Daniel P. KiehartAbstract:Actin filament crosslinking, bundling and Molecular Motor Proteins are necessary for the assembly of epithelial projections such as microvilli, stereocilia, hairs, and bristles. Mutations in such Proteins cause defects in the shape, structure, and function of these actin - based protrusions. One protein necessary for stereocilia formation, Myosin VIIA, is an actin - based Motor protein conserved throughout phylogeny. In Drosophila melanogaster, severe mutations in the MyoVIIA homolog crinkled (ck) are "semi - lethal" with only a very small percentage of flies surviving to adulthood. Such survivors show morphological defects related to actin bundling in hairs and bristles. To better understand ck/MyoVIIA's function in bundled - actin structures, we used dominant female sterile approaches to analyze the loss of maternal and zygotic (M/Z) ck/MyoVIIA in the morphogenesis of denticles, small actin - based projections on the ventral epidermis of Drosophila embryos. M/Z ck mutants displayed severe defects in denticle morphology - actin filaments initiated in the correct location, but failed to elongate and bundle to form normal projections. Using deletion mutant constructs, we demonstrated that both of the C - terminal MyTH4 and FERM domains are necessary for proper denticle formation. Furthermore, we show that ck/MyoVIIA interacts genetically with dusky - like (dyl), a member of the ZPD family of Proteins that links the extracellular matrix to the plasma membrane, and when mutated also disrupts normal denticle formation. Loss of either protein alone does not alter the localization of the other; however, loss of the two Proteins together dramatically enhances the defects in denticle shape observed when either protein alone was absent. Our data indicate that ck/MyoVIIA plays a key role in the formation and/or organization of actin filament bundles, which drive proper shape of cellular projections.
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Mutations in Drosophila crinkled/Myosin VIIA disrupt denticle morphogenesis.
Developmental biology, 2020Co-Authors: Jennifer L. Sallee, Janice M. Crawford, Vinay Singh, Daniel P. KiehartAbstract:Actin filament crosslinking, bundling and Molecular Motor Proteins are necessary for the assembly of epithelial projections such as microvilli, stereocilia, hairs, and bristles. Mutations in such Proteins cause defects in the shape, structure, and function of these actin - based protrusions. One protein necessary for stereocilia formation, Myosin VIIA, is an actin - based Motor protein conserved throughout phylogeny. In Drosophila melanogaster, severe mutations in the MyoVIIA homolog crinkled (ck) are "semi - lethal" with only a very small percentage of flies surviving to adulthood. Such survivors show morphological defects related to actin bundling in hairs and bristles. To better understand ck/MyoVIIA's function in bundled - actin structures, we used dominant female sterile approaches to analyze the loss of maternal and zygotic (M/Z) ck/MyoVIIA in the morphogenesis of denticles, small actin - based projections on the ventral epidermis of Drosophila embryos. M/Z ck mutants displayed severe defects in denticle morphology - actin filaments initiated in the correct location, but failed to elongate and bundle to form normal projections. Using deletion mutant constructs, we demonstrated that both of the C - terminal MyTH4 and FERM domains are necessary for proper denticle formation. Furthermore, we show that ck/MyoVIIA interacts genetically with dusky - like (dyl), a member of the ZPD family of Proteins that links the extracellular matrix to the plasma membrane, and when mutated also disrupts normal denticle formation. Loss of either protein alone does not alter the localization of the other; however, loss of the two Proteins together dramatically enhances the defects in denticle shape observed when either protein alone was absent. Our data indicate that ck/MyoVIIA plays a key role in the formation and/or organization of actin filament bundles, which drive proper shape of cellular projections.
Ambarish Kunwar - One of the best experts on this subject based on the ideXlab platform.
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Temperature-Dependent Activity of Motor Proteins: Energetics and Their Implications for Collective Behavior
Frontiers in Cell and Developmental Biology, 2021Co-Authors: Saumya Yadav, Ambarish KunwarAbstract:Molecular Motor Proteins are an extremely important component of the cellular transport system that harness chemical energy derived from ATP hydrolysis to carry out directed mechanical motion inside the cells. Transport properties of these Motors such as processivity, velocity, and their load dependence have been well established through single-molecule experiments. Temperature dependent biophysical properties of Molecular Motors are now being probed using single-molecule experiments. Additionally, the temperature dependent biochemical properties of Motors (ATPase activity) are probed to understand the underlying mechanisms and their possible implications on the enzymatic activity of Motor Proteins. These experiments in turn have revealed their activation energies and how they compare with the thermal energy available from the surrounding medium. In this review, we summarize such temperature dependent biophysical and biochemical properties of linear and rotary Motor Proteins and their implications for collective function during intracellular transport and cellular movement, respectively.
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Temperature-Dependent Activity of Motor Proteins: Energetics and Their Implications for Collective Behavior
Frontiers in cell and developmental biology, 2021Co-Authors: Saumya Yadav, Ambarish KunwarAbstract:Molecular Motor Proteins are extremely important components of cellular transport system that harness chemical energy derived from ATP hydrolysis to carry out directed mechanical motion inside the cells. Transport properties of these Motors such as processivity, velocity and their load dependence have been well established through single molecule experiments. Temperature dependence of biophysical properties of Molecular Motors are now being probed using single molecule experiments. These experiments in turn have revealed their activation energies and how they compare with the thermal energy available from surrounding medium. In this min-review, we summarize such temperature dependent properties of Motor Proteins and their implications for collective function during intra-cellular transport.
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Importance of anisotropy in detachment rates for force production and cargo transport by a team of Motor Proteins.
Protein science : a publication of the Protein Society, 2016Co-Authors: Anjneya Takshak, Ambarish KunwarAbstract:Many cellular processes are driven by collective forces generated by a team consisting of multiple Molecular Motor Proteins. One aspect that has received less attention is the detachment rate of Molecular Motors under mechanical force/load. While detachment rate of kinesin Motors measured under backward force increases rapidly for forces beyond stall-force; this scenario is just reversed for non-yeast dynein Motors where detachment rate from microtubule decreases, exhibiting a catch-bond type behavior. It has been shown recently that yeast dynein responds anisotropically to applied load, i.e. detachment rates are different under forward and backward pulling. Here, we use computational modeling to show that these anisotropic detachment rates might help yeast dynein Motors to improve their collective force generation in the absence of catch-bond behavior. We further show that the travel distance of cargos would be longer if detachment rates are anisotropic. Our results suggest that anisotropic detachment rates could be an alternative strategy for Motors to improve the transport properties and force production by the team.
Peter W. Baas - One of the best experts on this subject based on the ideXlab platform.
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Polarity Sorting of Microtubules in the Axon
Trends in neurosciences, 2017Co-Authors: Anand N. Rao, Peter W. BaasAbstract:A longstanding question in cellular neuroscience is how microtubules in the axon become organized with their plus ends out, a pattern starkly different from the mixed orientation of microtubules in vertebrate dendrites. Recent attention has focused on a mechanism called polarity sorting, in which microtubules of opposite orientation are spatially separated by Molecular Motor Proteins. Here we discuss this mechanism, and conclude that microtubules are polarity sorted in the axon by cytoplasmic dynein but that additional factors are also needed. In particular, computational modeling and experimental evidence suggest that static crosslinking Proteins are required to appropriately restrict microtubule movements so that polarity sorting by cytoplasmic dynein can occur in a manner unimpeded by other Motor Proteins.
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Microtubules and Growth Cones: Motors Drive the Turn
Trends in neurosciences, 2016Co-Authors: Olga I. Kahn, Peter W. BaasAbstract:Navigation of the growth cone at the tip of the developing axon is crucial for the proper wiring of the nervous system. Mechanisms of actin-dependent growth cone steering, via signaling cascades, are well documented. Microtubules are also important in growth cone guidance, because their polarized invasion into the peripheral domain on one side of the growth cone is essential for it to turn in that direction. Classically, microtubules have been considered secondary players, invading the peripheral domain only where the actin cytoskeleton permits them to go. Presented here is evidence for an underappreciated mechanism by which signaling cascades can potentially affect growth cone turning, namely through regulatable forces imposed on the microtubules by Molecular Motor Proteins.
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Beyond taxol: microtubule-based treatment of disease and injury of the nervous system
Brain, 2013Co-Authors: Peter W. Baas, Fridoon Jawad AhmadAbstract:Contemporary research has revealed a great deal of information on the behaviours of microtubules that underlie critical events in the lives of neurons. Microtubules in the neuron undergo dynamic assembly and disassembly, bundling and splaying, severing, and rapid transport as well as integration with other cytoskeletal elements such as actin filaments. These various behaviours are regulated by signalling pathways that affect microtubule-related Proteins such as Molecular Motor Proteins and microtubule severing enzymes, as well as a variety of Proteins that promote the assembly, stabilization and bundling of microtubules. In recent years, translational neuroscientists have earmarked microtubules as a promising target for therapy of injury and disease of the nervous system. Proof-of-principle has come mainly from studies using taxol and related drugs to pharmacologically stabilize microtubules in animal models of nerve injury and disease. However, concerns persist that the negative consequences of abnormal microtubule stabilization may outweigh the positive effects. Other potential approaches include microtubule-active drugs with somewhat different properties, but also expanding the therapeutic toolkit to include intervention at the level of microtubule regulatory Proteins.
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Microtubule–Actin Interactions During Neuronal Development
Advances in Neurobiology, 2010Co-Authors: Kenneth A. Myers, Peter W. BaasAbstract:Neuronal development involves many morphological changes and events that are intimately dependent upon microtubules. These include neuronal migration, axonal and dendritic differentiation, growth, and branching, the navigation of the axon to its target, and the retraction of overgrown axons. Within the various compartments of developing neurons, microtubules take on a variety of different lengths and configurations, and undergo behaviors such as dynamic assembly and disassembly, stabilization, and transport. A growing body of evidence suggests that the microtubule behaviors that underlie neuronal morphogenesis may be regulated in part by interactions of the microtubules with the actin cytoskeleton. The purpose of this chapter is to provide an overview of some of these microtubule–actin interactions and to discuss how these interactions may be important during the development of the neuron. The chapter includes discussions on signaling pathways, Molecular Motor Proteins, classical and non-classical microtubule-associated Proteins, and +TIPS.
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Critical roles for microtubules in axonal development and disease.
Results and problems in cell differentiation, 2009Co-Authors: Aditi Falnikar, Peter W. BaasAbstract:Axons are occupied by dense arrays of cytoskeletal elements called microtubules, which are critical for generating and maintaining the architecture of the axon, and for acting as railways for the transport of organelles in both directions within the axon. Microtubules are organized and regulated by molecules that affect their assembly and disassembly, their stabilization, their association with other cytoskeletal elements, and their alignment and bundling with one another. Recent studies have accentuated the role of Molecular Motor Proteins and microtubule-severing Proteins in the establishment and maintenance of the axonal microtubule array. The growing body of knowledge on the Proteins and mechanisms that regulate axonal microtubules has fostered a better understanding of how many debilitating diseases cause axons to degenerate. The purpose of this chapter is to provide an update on current knowledge of axonal microtubules and the Proteins that regulate them, and to reflect on cutting-edge findings linking these Proteins and mechanisms to diseases that afflict the human population.
Vinay Singh - One of the best experts on this subject based on the ideXlab platform.
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mutations in drosophila crinkled myosin viia disrupt denticle morphogenesis
Developmental Biology, 2021Co-Authors: Janice M. Crawford, Jennifer L. Sallee, Vinay Singh, Daniel P. KiehartAbstract:Actin filament crosslinking, bundling and Molecular Motor Proteins are necessary for the assembly of epithelial projections such as microvilli, stereocilia, hairs, and bristles. Mutations in such Proteins cause defects in the shape, structure, and function of these actin - based protrusions. One protein necessary for stereocilia formation, Myosin VIIA, is an actin - based Motor protein conserved throughout phylogeny. In Drosophila melanogaster, severe mutations in the MyoVIIA homolog crinkled (ck) are "semi - lethal" with only a very small percentage of flies surviving to adulthood. Such survivors show morphological defects related to actin bundling in hairs and bristles. To better understand ck/MyoVIIA's function in bundled - actin structures, we used dominant female sterile approaches to analyze the loss of maternal and zygotic (M/Z) ck/MyoVIIA in the morphogenesis of denticles, small actin - based projections on the ventral epidermis of Drosophila embryos. M/Z ck mutants displayed severe defects in denticle morphology - actin filaments initiated in the correct location, but failed to elongate and bundle to form normal projections. Using deletion mutant constructs, we demonstrated that both of the C - terminal MyTH4 and FERM domains are necessary for proper denticle formation. Furthermore, we show that ck/MyoVIIA interacts genetically with dusky - like (dyl), a member of the ZPD family of Proteins that links the extracellular matrix to the plasma membrane, and when mutated also disrupts normal denticle formation. Loss of either protein alone does not alter the localization of the other; however, loss of the two Proteins together dramatically enhances the defects in denticle shape observed when either protein alone was absent. Our data indicate that ck/MyoVIIA plays a key role in the formation and/or organization of actin filament bundles, which drive proper shape of cellular projections.
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Mutations in Drosophila crinkled/Myosin VIIA disrupt denticle morphogenesis.
Developmental biology, 2020Co-Authors: Jennifer L. Sallee, Janice M. Crawford, Vinay Singh, Daniel P. KiehartAbstract:Actin filament crosslinking, bundling and Molecular Motor Proteins are necessary for the assembly of epithelial projections such as microvilli, stereocilia, hairs, and bristles. Mutations in such Proteins cause defects in the shape, structure, and function of these actin - based protrusions. One protein necessary for stereocilia formation, Myosin VIIA, is an actin - based Motor protein conserved throughout phylogeny. In Drosophila melanogaster, severe mutations in the MyoVIIA homolog crinkled (ck) are "semi - lethal" with only a very small percentage of flies surviving to adulthood. Such survivors show morphological defects related to actin bundling in hairs and bristles. To better understand ck/MyoVIIA's function in bundled - actin structures, we used dominant female sterile approaches to analyze the loss of maternal and zygotic (M/Z) ck/MyoVIIA in the morphogenesis of denticles, small actin - based projections on the ventral epidermis of Drosophila embryos. M/Z ck mutants displayed severe defects in denticle morphology - actin filaments initiated in the correct location, but failed to elongate and bundle to form normal projections. Using deletion mutant constructs, we demonstrated that both of the C - terminal MyTH4 and FERM domains are necessary for proper denticle formation. Furthermore, we show that ck/MyoVIIA interacts genetically with dusky - like (dyl), a member of the ZPD family of Proteins that links the extracellular matrix to the plasma membrane, and when mutated also disrupts normal denticle formation. Loss of either protein alone does not alter the localization of the other; however, loss of the two Proteins together dramatically enhances the defects in denticle shape observed when either protein alone was absent. Our data indicate that ck/MyoVIIA plays a key role in the formation and/or organization of actin filament bundles, which drive proper shape of cellular projections.