The Experts below are selected from a list of 318 Experts worldwide ranked by ideXlab platform
Jessica L. Feldman - One of the best experts on this subject based on the ideXlab platform.
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centriole less pericentriolar material serves as a Microtubule Organizing Center at the base of c elegans sensory cilia
Current Biology, 2021Co-Authors: Jérémy Magescas, Sani Eskinazi, Michael V. Tran, Jessica L. FeldmanAbstract:Summary During mitosis in animal cells, the centrosome acts as a Microtubule Organizing Center (MTOC) to assemble the mitotic spindle. MTOC function at the centrosome is driven by proteins within the pericentriolar material (PCM), however the molecular complexity of the PCM makes it difficult to differentiate the proteins required for MTOC activity from other centrosomal functions. We used the natural spatial separation of PCM proteins during mitotic exit to identify a minimal module of proteins required for centrosomal MTOC function in C. elegans. Using tissue-specific degradation, we show that SPD-5, the functional homolog of CDK5RAP2, is essential for embryonic mitosis, while SPD-2/CEP192 and PCMD-1, which are essential in the one-cell embryo, are dispensable. Surprisingly, although the centriole is known to be degraded in the ciliated sensory neurons in C. elegans,1–3 we find evidence for "centriole-less PCM" at the base of cilia and use this structure as a minimal testbed to dissect centrosomal MTOC function. Super-resolution imaging revealed that this PCM inserts inside the lumen of the ciliary axoneme and directly nucleates the assembly of dendritic Microtubules toward the cell body. Tissue-specific degradation in ciliated sensory neurons revealed a role for SPD-5 and the conserved Microtubule nucleator γ-TuRC, but not SPD-2 or PCMD-1, in MTOC function at centriole-less PCM. This MTOC function was in the absence of regulation by mitotic kinases, highlighting the intrinsic ability of these proteins to drive Microtubule growth and organization and further supporting a model that SPD-5 is the primary driver of MTOC function at the PCM.
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centriole less pericentriolar material serves as a Microtubule Organizing Center at the base of c elegans sensory cilia
Social Science Research Network, 2020Co-Authors: Jérémy Magescas, Sani Eskinazi, Michael V. Tran, Jessica L. FeldmanAbstract:During mitosis in animal cells, the centrosome acts as a Microtubule Organizing Center (MTOC) to assemble the mitotic spindle. MTOC function at the centrosome is driven by proteins within the pericentriolar material (PCM), however the molecular complexity of the PCM makes it difficult to differentiate the proteins required for MTOC activity from other centrosomal functions. We used the natural spatial separation of PCM proteins during mitotic exit to identify a minimal module of proteins required for centrosomal MTOC function in C. elegans. Using tissue specific degradation, we show that SPD-5, the functional homolog of CDK5RAP2, is essential for embryonic mitosis while SPD-2/CEP192 and PCMD-1, which are essential in the zygote, are dispensable. Surprisingly, although the centriole is known to be degraded in the ciliated sensory neurons in C. elegans , we find evidence for “centriole-less PCM” at the base of cilia and use this structure as a minimal testbed to dissect centrosomal MTOC function. Super-resolution imaging revealed that this PCM inserts inside the lumen of the ciliary axoneme and directly nucleates the assembly of dendritic Microtubules towards the cell body. Tissue-specific degradation in ciliated sensory neurons revealed a role for SPD-5 and the conserved Microtubule nucleator [[EQUATION]] -TuRC, but not SPD-2 or PCMD-1, in MTOC function at centriole-less PCM. This MTOC function was in the absence of regulation by mitotic kinases, highlighting the intrinsic ability of these proteins to drive Microtubule growth and organization and further supporting a model that SPD-5 is the primary driver of MTOC function at the PCM.
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Centriole-less pericentriolar material serves as a Microtubule Organizing Center at the base of C. elegans sensory cilia
bioRxiv, 2020Co-Authors: Jérémy Magescas, Sani Eskinazi, Michael V. Tran, Jessica L. FeldmanAbstract:During mitosis in animal cells, the centrosome acts as a Microtubule Organizing Center (MTOC) to assemble the mitotic spindle. MTOC function at the centrosome is driven by proteins within the pericentriolar material (PCM), however the molecular complexity of the PCM makes it difficult to differentiate the proteins required for MTOC activity from other centrosomal functions. We used the natural spatial separation of PCM proteins during mitotic exit to identify a minimal module of proteins required for centrosomal MTOC function in C. elegans. Using tissue specific degradation, we show that SPD-5, the functional homolog of CDK5RAP2, is essential for embryonic mitosis while SPD-2/CEP192 and PCMD-1, which are essential in the zygote, are dispensable. Surprisingly, although the centriole is known to be degraded in the ciliated sensory neurons in C. elegans [1-3], we find evidence for "centriole-less PCM" at the base of cilia and use this structure as a minimal testbed to dissect centrosomal MTOC function. Super-resolution imaging revealed that this PCM inserts inside the lumen of the ciliary axoneme and directly nucleates the assembly of dendritic Microtubules towards the cell body. Tissue-specific degradation in ciliated sensory neurons revealed a role for SPD-5 and the conserved Microtubule nucleator {gamma}-TuRC, but not SPD-2 or PCMD-1, in MTOC function at centriole-less PCM. This MTOC function was in the absence of regulation by mitotic kinases, highlighting the intrinsic ability of these proteins to drive Microtubule growth and organization and further supporting a model that SPD-5 is the primary driver of MTOC function at the PCM.
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growth cone localized Microtubule Organizing Center establishes Microtubule orientation in dendrites
eLife, 2020Co-Authors: Jessica L. Feldman, Xing Liang, Marcela Kokes, Richard D Fetter, Maria D Sallee, Adrian W Moore, Kang ShenAbstract:A polarized arrangement of neuronal Microtubule arrays is the foundation of membrane trafficking and subcellular compartmentalization. Conserved among both invertebrates and vertebrates, axons contain exclusively 'plus-end-out' Microtubules while dendrites contain a high percentage of 'minus-end-out' Microtubules, the origins of which have been a mystery. Here we show that in Caenorhabditis elegans the dendritic growth cone contains a non-centrosomal Microtubule Organizing Center (MTOC), which generates minus-end-out Microtubules along outgrowing dendrites and plus-end-out Microtubules in the growth cone. RAB-11-positive endosomes accumulate in this region and co-migrate with the Microtubule nucleation complex γ-TuRC. The MTOC tracks the extending growth cone by kinesin-1/UNC-116-mediated endosome movements on distal plus-end-out Microtubules and dynein clusters this advancing MTOC. Critically, perturbation of the function or localization of the MTOC causes reversed Microtubule polarity in dendrites. These findings unveil the endosome-localized dendritic MTOC as a critical organelle for establishing axon-dendrite polarity.
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growth cone localized Microtubule Organizing Center establishes Microtubule orientation in dendrites
2020Co-Authors: Xing Liang, Jessica L. Feldman, Marcela Kokes, Richard D Fetter, Maria D Sallee, Adrian W Moore, Kang ShenAbstract:A polarized arrangement of neuronal Microtubule arrays is the foundation of membrane trafficking and subcellular compartmentalization. Conserved among both invertebrates and vertebrates, axons contain exclusively “plus-end-out” Microtubules while dendrites contain a high percentage of “minus-end-out” Microtubules, the origins of which have been a mystery. Here we show that the dendritic growth cone contains a non-centrosomal Microtubule Organizing Center, which generates minus-end-out Microtubules along outgrowing dendrites and plus-end-out Microtubules in the growth cone. RAB-11-positive endosomes accumulate in this region and are responsible for localizing the Microtubule nucleation complex γ-TuRC. The MTOC tracks the extending growth cone by kinesin-1/UNC-116-mediated endosome movements on distal plus-end-out Microtubules and dynein clusters this advancing MTOC. Critically, perturbation of the function or localization of the MTOC causes reversed Microtubule polarity in dendrites. These findings unveil the dendritic MTOC as a critical organelle for establishing axon-dendrite polarity.
Michael R. Gold - One of the best experts on this subject based on the ideXlab platform.
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The Rap2c GTPase facilitates B cell receptor-induced reorientation of the Microtubule-Organizing Center.
Small GTPases, 2018Co-Authors: Jia C. Wang, Jeff Y.-j. Lee, May Dang-lawson, Caitlin Pritchard, Michael R. GoldAbstract:When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR) signaling initiates remodeling of the F-actin network and reorientation of the Microtubule-Organizing Center (MTOC) towa...
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the rap2c gtpase facilitates b cell receptor induced reorientation of the Microtubule Organizing Center
Small GTPases, 2018Co-Authors: Jia C. Wang, Jeff Y.-j. Lee, Caitlin Pritchard, May Danglawson, Michael R. GoldAbstract:When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR) signaling initiates remodeling of the F-actin network and reorientation of the Microtubule-Organizing Center (MTOC) towards the antigen contact site. We have previously shown that the Rap1 GTPase, an evolutionarily conserved regulator of cell polarity, is essential for these processes and that Rap1-regulated actin remodeling is required for MTOC polarization. The role of Rap2 proteins in establishing cell polarity is not well understood. We now show that depleting Rap2c, the only Rap2 isoform expressed in the A20 B-cell line, impairs BCR-induced MTOC reorientation as well as the actin remodeling that supports MTOC polarization. Thus Rap1 and Rap2 proteins may have similar but non-redundant functions in coupling the BCR to MTOC polarization.
Jia C. Wang - One of the best experts on this subject based on the ideXlab platform.
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The Rap2c GTPase facilitates B cell receptor-induced reorientation of the Microtubule-Organizing Center.
Small GTPases, 2018Co-Authors: Jia C. Wang, Jeff Y.-j. Lee, May Dang-lawson, Caitlin Pritchard, Michael R. GoldAbstract:When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR) signaling initiates remodeling of the F-actin network and reorientation of the Microtubule-Organizing Center (MTOC) towa...
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the rap2c gtpase facilitates b cell receptor induced reorientation of the Microtubule Organizing Center
Small GTPases, 2018Co-Authors: Jia C. Wang, Jeff Y.-j. Lee, Caitlin Pritchard, May Danglawson, Michael R. GoldAbstract:When B lymphocytes encounter antigen-bearing surfaces, B-cell receptor (BCR) signaling initiates remodeling of the F-actin network and reorientation of the Microtubule-Organizing Center (MTOC) towards the antigen contact site. We have previously shown that the Rap1 GTPase, an evolutionarily conserved regulator of cell polarity, is essential for these processes and that Rap1-regulated actin remodeling is required for MTOC polarization. The role of Rap2 proteins in establishing cell polarity is not well understood. We now show that depleting Rap2c, the only Rap2 isoform expressed in the A20 B-cell line, impairs BCR-induced MTOC reorientation as well as the actin remodeling that supports MTOC polarization. Thus Rap1 and Rap2 proteins may have similar but non-redundant functions in coupling the BCR to MTOC polarization.
Jérémy Magescas - One of the best experts on this subject based on the ideXlab platform.
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centriole less pericentriolar material serves as a Microtubule Organizing Center at the base of c elegans sensory cilia
Current Biology, 2021Co-Authors: Jérémy Magescas, Sani Eskinazi, Michael V. Tran, Jessica L. FeldmanAbstract:Summary During mitosis in animal cells, the centrosome acts as a Microtubule Organizing Center (MTOC) to assemble the mitotic spindle. MTOC function at the centrosome is driven by proteins within the pericentriolar material (PCM), however the molecular complexity of the PCM makes it difficult to differentiate the proteins required for MTOC activity from other centrosomal functions. We used the natural spatial separation of PCM proteins during mitotic exit to identify a minimal module of proteins required for centrosomal MTOC function in C. elegans. Using tissue-specific degradation, we show that SPD-5, the functional homolog of CDK5RAP2, is essential for embryonic mitosis, while SPD-2/CEP192 and PCMD-1, which are essential in the one-cell embryo, are dispensable. Surprisingly, although the centriole is known to be degraded in the ciliated sensory neurons in C. elegans,1–3 we find evidence for "centriole-less PCM" at the base of cilia and use this structure as a minimal testbed to dissect centrosomal MTOC function. Super-resolution imaging revealed that this PCM inserts inside the lumen of the ciliary axoneme and directly nucleates the assembly of dendritic Microtubules toward the cell body. Tissue-specific degradation in ciliated sensory neurons revealed a role for SPD-5 and the conserved Microtubule nucleator γ-TuRC, but not SPD-2 or PCMD-1, in MTOC function at centriole-less PCM. This MTOC function was in the absence of regulation by mitotic kinases, highlighting the intrinsic ability of these proteins to drive Microtubule growth and organization and further supporting a model that SPD-5 is the primary driver of MTOC function at the PCM.
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centriole less pericentriolar material serves as a Microtubule Organizing Center at the base of c elegans sensory cilia
Social Science Research Network, 2020Co-Authors: Jérémy Magescas, Sani Eskinazi, Michael V. Tran, Jessica L. FeldmanAbstract:During mitosis in animal cells, the centrosome acts as a Microtubule Organizing Center (MTOC) to assemble the mitotic spindle. MTOC function at the centrosome is driven by proteins within the pericentriolar material (PCM), however the molecular complexity of the PCM makes it difficult to differentiate the proteins required for MTOC activity from other centrosomal functions. We used the natural spatial separation of PCM proteins during mitotic exit to identify a minimal module of proteins required for centrosomal MTOC function in C. elegans. Using tissue specific degradation, we show that SPD-5, the functional homolog of CDK5RAP2, is essential for embryonic mitosis while SPD-2/CEP192 and PCMD-1, which are essential in the zygote, are dispensable. Surprisingly, although the centriole is known to be degraded in the ciliated sensory neurons in C. elegans , we find evidence for “centriole-less PCM” at the base of cilia and use this structure as a minimal testbed to dissect centrosomal MTOC function. Super-resolution imaging revealed that this PCM inserts inside the lumen of the ciliary axoneme and directly nucleates the assembly of dendritic Microtubules towards the cell body. Tissue-specific degradation in ciliated sensory neurons revealed a role for SPD-5 and the conserved Microtubule nucleator [[EQUATION]] -TuRC, but not SPD-2 or PCMD-1, in MTOC function at centriole-less PCM. This MTOC function was in the absence of regulation by mitotic kinases, highlighting the intrinsic ability of these proteins to drive Microtubule growth and organization and further supporting a model that SPD-5 is the primary driver of MTOC function at the PCM.
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Centriole-less pericentriolar material serves as a Microtubule Organizing Center at the base of C. elegans sensory cilia
bioRxiv, 2020Co-Authors: Jérémy Magescas, Sani Eskinazi, Michael V. Tran, Jessica L. FeldmanAbstract:During mitosis in animal cells, the centrosome acts as a Microtubule Organizing Center (MTOC) to assemble the mitotic spindle. MTOC function at the centrosome is driven by proteins within the pericentriolar material (PCM), however the molecular complexity of the PCM makes it difficult to differentiate the proteins required for MTOC activity from other centrosomal functions. We used the natural spatial separation of PCM proteins during mitotic exit to identify a minimal module of proteins required for centrosomal MTOC function in C. elegans. Using tissue specific degradation, we show that SPD-5, the functional homolog of CDK5RAP2, is essential for embryonic mitosis while SPD-2/CEP192 and PCMD-1, which are essential in the zygote, are dispensable. Surprisingly, although the centriole is known to be degraded in the ciliated sensory neurons in C. elegans [1-3], we find evidence for "centriole-less PCM" at the base of cilia and use this structure as a minimal testbed to dissect centrosomal MTOC function. Super-resolution imaging revealed that this PCM inserts inside the lumen of the ciliary axoneme and directly nucleates the assembly of dendritic Microtubules towards the cell body. Tissue-specific degradation in ciliated sensory neurons revealed a role for SPD-5 and the conserved Microtubule nucleator {gamma}-TuRC, but not SPD-2 or PCMD-1, in MTOC function at centriole-less PCM. This MTOC function was in the absence of regulation by mitotic kinases, highlighting the intrinsic ability of these proteins to drive Microtubule growth and organization and further supporting a model that SPD-5 is the primary driver of MTOC function at the PCM.
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a two step mechanism for the inactivation of Microtubule Organizing Center function at the centrosome
eLife, 2019Co-Authors: Jérémy Magescas, Jennifer C Zonka, Jessica L. FeldmanAbstract:The centrosome acts as a Microtubule Organizing Center (MTOC), orchestrating Microtubules into the mitotic spindle through its pericentriolar material (PCM). This activity is biphasic, cycling through assembly and disassembly during the cell cycle. Although hyperactive centrosomal MTOC activity is a hallmark of some cancers, little is known about how the centrosome is inactivated as an MTOC. Analysis of endogenous PCM proteins in C. elegans revealed that the PCM is composed of partially overlapping territories organized into an inner and outer sphere that are removed from the centrosome at different rates and using different behaviors. We found that phosphatases oppose the addition of PCM by mitotic kinases, ultimately catalyzing the dissolution of inner sphere PCM proteins at the end of mitosis. The nature of the PCM appears to change such that the remaining aging PCM outer sphere is mechanically ruptured by cortical pulling forces, ultimately inactivating MTOC function at the centrosome.
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a two step mechanism for the inactivation of Microtubule Organizing Center function at the centrosome
bioRxiv, 2018Co-Authors: Jérémy Magescas, Jennifer C Zonka, Jessica L. FeldmanAbstract:During mitosis, the centrosome acts as a Microtubule Organizing Center (MTOC), orchestrating Microtubules into the mitotic spindle through its pericentriolar material (PCM). This activity is biphasic, cycling through assembly and disassembly during the cell cycle. Although hyperactive centrosomal MTOC activity is a hallmark of some cancers, little is known about how the centrosome is inactivated as an MTOC. Analysis of endogenous PCM proteins in C. elegans revealed that the PCM is composed of distinct protein territories that are removed from the centrosome at different rates and using different behaviors. Inhibition of PP2A phosphatases stabilized the PCM and perturbation of cortical pulling forces altered the timing and behavior by which proteins were removed from the centrosome. These data indicate that PCM disassembly is a two-step process, beginning with a phosphatase-dependent dissolution of PCM proteins followed by the ejection of ruptured PCM by cortical forces, ultimately inactivating MTOC function at the centrosome.
Conly L. Rieder - One of the best experts on this subject based on the ideXlab platform.
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Reproductive capacity of sea urchin centrosomes without centrioles
Cytoskeleton, 2005Co-Authors: Greenfield Sluder, Frederick J. Miller, Conly L. RiederAbstract:For animal cells, the relative roles of the centrioles and the pericentriolar material (the centrosomal Microtubule Organizing Center) in controlling the precise doubling of the centrosome before mitosis have not been well defined. To this end we devised an experimental system that allowed us to characterize the capacity of the centrosomal Microtubule Organizing Center to double regularly in the absence of centrioles. Sea urchin eggs were fertilized, stripped of their fertilization envelopes, and fragmented before syngamy. Those activated egg fragments containing just the female pronucleus assembled a monaster at first mitosis. A serial section ultrastructural analysis of such monasters revealed that the radially arrayed Microtubules were organized by a hollow fenestrated sphere of electron-dense material, of the same appearance as pericentriolar material, that was devoid of centrioles. We followed individual fragments with only a female pronucleus through at least three cell cycles and found that the monasters did not double between mitoses. The observation that fragments with only a male pronucleus repeatedly divided in a normal fashion indicates that the assembly and behavior of monasters were not artifacts of egg fragmentation. Our results demonstrate that the activity that controls the precise doubling of the centrosome before mitosis is distinct and experimentally separable from the centrosomal Microtubule Organizing Center. Our observations also extend the correlation between the reproductive capacity of a centrosome and the number of centrioles it contains (G Sluder and CL Rieder, 1985a: J. Cell Biol. 100:887-896). For a cell that normally has centrioles, we show that a centrosome without centrioles does not reproduce between mitoses.
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the centrosome in vertebrates more than a Microtubule Organizing Center
Trends in Cell Biology, 2001Co-Authors: Conly L. Rieder, Shamsa Faruki, Alexey KhodjakovAbstract:The somatic cells of all higher animals contain a single minute organelle called the centrosome. For years, the functions of the centrosome were thought to revolve around its ability to nucleate and organize the various Microtubule arrays seen in interphase and mitosis. But the centrosome is more than just a Microtubule-Organizing Center. Recent work reveals that this organelle is essential for cell-cycle progression and that this requirement is independent of its ability to organize Microtubules. Here, we review the various functions attributed to the centrosome and ask which are essential for the survival and reproduction of the cell, the organism, or both.