المؤلفون: Yuhan Hu, Annika G. Samuelson, Alexandra Magee, Laura Anne Lowery, Garrett M. Cammarata, Paula G. Slater

المصدر: J Cell Sci

مصطلحات موضوعية: CKAP5, Growth Cones, Xenopus, macromolecular substances, Xenopus Proteins, Biology, Microtubules, Xenopus laevis, 03 medical and health sciences, 0302 clinical medicine, Microtubule, Animals, Cytoskeleton, Growth cone, Actin, 030304 developmental biology, 0303 health sciences, Cell Biology, biology.organism_classification, Ephrin-A5, Actins, Axons, Axon Guidance, Cell biology, Actin Cytoskeleton, Axon guidance, Ephrin A5, Microtubule-Associated Proteins, 030217 neurology & neurosurgery, Research Article

الوصف: It has long been established that neuronal growth cone navigation depends on changes in microtubule (MT) and F-actin architecture downstream of guidance cues. However, the mechanisms by which MTs and F-actin are dually coordinated remain a fundamentally unresolved question. Here, we report that the well-characterized MT polymerase, XMAP215 (also known as CKAP5), plays an important role in mediating MT–F-actin interaction within the growth cone. We demonstrate that XMAP215 regulates MT–F-actin alignment through its N-terminal TOG 1–5 domains. Additionally, we show that XMAP215 directly binds to F-actin in vitro and co-localizes with F-actin in the growth cone periphery. We also find that XMAP215 is required for regulation of growth cone morphology and response to the guidance cue, Ephrin A5. Our findings provide the first strong evidence that XMAP215 coordinates MT and F-actin interaction in vivo. We suggest a model in which XMAP215 regulates MT extension along F-actin bundles into the growth cone periphery and that these interactions may be important to control cytoskeletal dynamics downstream of guidance cues. This article has an associated First Person interview with the first author of the paper.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::481b06ec873007340df32b05c183944fTest
https://doi.org/10.1242/jcs.224311Test

المؤلفون: Kundu, Tanushree, Dutta, Priyanka, Nagar, Dhriti, Maiti, Sankar, Ghose, Aurnab

المصدر: Journal of Cell Science; Jul2021, Vol. 134 Issue 13, p1-1, 1p

مصطلحات موضوعية: F-actin, MICROTUBULES, CHEMOTAXIS, HIGH resolution imaging, CONES, FILOPODIA

مستخلص: Dynamic co-regulation of the actin and microtubule subsystems enables the highly precise and adaptive remodelling of the cytoskeleton necessary for critical cellular processes, such as axonal pathfinding. The modes and mediators of this interpolymer crosstalk, however, are inadequately understood. We identify Fmn2, a non-diaphanous-related formin associated with cognitive disabilities, as a novel regulator of cooperative microtubule remodelling in growth cones of both chick and zebrafish neurons. We show that Fmn2 stabilizes microtubules in the growth cones of cultured spinal neurons and in vivo. Super-resolution imaging revealed that Fmn2 facilitates guidance of exploratory microtubules along actin bundles into the chemosensory filopodia. Using live imaging, biochemistry and single-molecule assays, we show that a C-terminal domain in Fmn2 is necessary for the dynamic association between microtubules and actin filaments. In the absence of the cross-bridging function of Fmn2, filopodial capture of microtubules is compromised, resulting in destabilized filopodial protrusions and deficits in growth cone chemotaxis. Our results uncover a critical function for Fmn2 in microtubule crosstalk in neurons and demonstrate that the modulation of microtubule dynamics via associations with F-actin is central to directional motility. [ABSTRACT FROM AUTHOR]

: Copyright of Journal of Cell Science is the property of Company of Biologists Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Sara Geraldo, Phillip R. Gordon-Weeks

المصدر: Journal of Cell Science. 122:3595-3604

مصطلحات موضوعية: Dendritic spine, genetic structures, biology, Dendritic Spines, Growth Cones, Arp2/3 complex, macromolecular substances, Cell Biology, Microtubules, Actins, Cell biology, Actin remodeling of neurons, Treadmilling, Commentary, biology.protein, Animals, Humans, Axon guidance, sense organs, Cytoskeleton, Growth cone, Filopodia, Signal Transduction

الوصف: Interactions between dynamic microtubules and actin filaments are essential to a wide range of cell biological processes including cell division, motility and morphogenesis. In neuronal growth cones, interactions between microtubules and actin filaments in filopodia are necessary for growth cones to make a turn. Growth-cone turning is a fundamental behaviour during axon guidance, as correct navigation of the growth cone through the embryo is required for it to locate an appropriate synaptic partner. Microtubule-actin filament interactions also occur in the transition zone and central domain of the growth cone, where actin arcs exert compressive forces to corral microtubules into the core of the growth cone and thereby facilitate microtubule bundling, a requirement for axon formation. We now have a fairly comprehensive understanding of the dynamic behaviour of the cytoskeleton in growth cones, and the stage is set for discovering the molecular machinery that enables microtubule-actin filament coupling in growth cones, as well as the intracellular signalling pathways that regulate these interactions. Furthermore, recent experiments suggest that microtubule-actin filament interactions might also be important for the formation of dendritic spines from filopodia in mature neurons. Therefore, the mechanisms coupling microtubules to actin filaments in growth-cone turning and dendritic-spine maturation might be conserved.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::90cae1b46df466411380e03ffe2a0755Test
https://doi.org/10.1242/jcs.042309Test

المؤلفون: Ann M. Rajnicek, Louise E. Foubister, Colin D. McCaig

المصدر: Journal of Cell Science. 119:1736-1745

مصطلحات موضوعية: Growth Cones, macromolecular substances, CDC42, Biology, Microfilament, Microtubules, Xenopus laevis, chemistry.chemical_compound, Electricity, Cell Movement, Animals, Humans, Pseudopodia, Enzyme Inhibitors, cdc42 GTP-Binding Protein, Growth cone, Cell Shape, Electrodes, Cells, Cultured, Neurons, Cell Biology, Actins, rac GTP-Binding Proteins, Cell biology, Actin Cytoskeleton, Nocodazole, Spinal Cord, chemistry, Latrunculin, Axon guidance, Lamellipodium, Filopodia

الوصف: Electric fields (EFs) resembling those in the developing and regenerating nervous systems steer growth cones towards the cathode. Requirements for actin microfilaments, microtubules and their interactions during EF growth cone steering have been presumed, but remain unproven. Here, we demonstrate essential roles for dynamic microfilaments and microtubules in cathode-directed migration. Cathodal turning of growth cones on cultured Xenopus embryonic spinal neurons was attenuated significantly by nanomolar concentrations of the microfilament inhibitor latrunculin, the microtubule-stabilising drug taxol, or the microtubule-destabilising drugs vinblastine or nocodazole. Dynamically, the cathodal bias of filopodia preceded cathodal turning of the growth cone, suggesting an instructive role in EF-induced steering. Lamellipodial asymmetry accompanied turning. Filopodia and lamellipodia are regulated by the GTPases Cdc42 and Rac, respectively, and, as shown in the companion paper in this issue, peptides that selectively prevented effector binding to the CRIB domains of Cdc42 or Rac abolished cathodal growth cone turning during 3 hours of EF exposure. Here, the Rac peptide suppressed lamellipodium formation, increased the number of filopodia, abolished cathodal filopodial orientation, and prevented cathodal steering. The Cdc42 peptide suppressed filopodium formation, increased lamellipodial area and prevented cathodal steering. The cathodal bias of lamellipodia was independent of Cdc42 CRIB activity and was not sufficient for cathodal steering in the absence of filopodia, but the cathodal bias of filopodia through Rac CRIB activity was necessary for cathodal turning. Understanding the mechanism for cathodal growth cone guidance will enhance the emerging clinical effort to stimulate human spinal cord regeneration through EF application.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::13642ae41a0bc1856d2616ec1f1690f2Test
https://doi.org/10.1242/jcs.02897Test

المؤلفون: Gareth E. Jones, Mark R. Holt, Britta J. Eickholt, Aminul I. Ahmed, Neil H Chadborn, Graham Dunn, Rabinder Kumar Prinjha

المصدر: Journal of Cell Science. 119:951-957

مصطلحات موضوعية: Morpholines, Growth Cones, Chick Embryo, Microtubules, Glycogen Synthase Kinase 3, Phosphatidylinositol 3-Kinases, Semaphorin, medicine, Animals, PTEN, Axon, Growth cone, Cells, Cultured, PI3K/AKT/mTOR pathway, Phosphoinositide-3 Kinase Inhibitors, Neurons, Growth cone membrane, biology, PTEN Phosphohydrolase, Semaphorin-3A, SEMA3A, Cell Biology, Cell biology, medicine.anatomical_structure, Chromones, biology.protein, Axon guidance, Signal Transduction

الوصف: Distinct changes in glycogen synthase kinase-3 (GSK-3) signalling can regulate neuronal morphogenesis including the determination and maintenance of axonal identity, and are required for neurotrophin-mediated axon elongation. In addition, we have previously shown a dependency on GSK-3 activation in the semaphorin 3A (Sema3A)-mediated growth-cone-collapse response of sensory neurons. Regulation of GSK-3 activity involves the intermediate signalling lipid phosphatidylinositol 3,4,5-trisphosphate, which can be modulated by phosphatidylinositol 3-kinase (PI3K) and the tumour suppressor PTEN. We report here the involvement of PTEN in the Sema3A-mediated growth cone collapse. Sema3A suppresses PI3K signalling concomitant with the activation of GSK-3, which depends on the phosphatase activity of PTEN. PTEN is highly enriched in the axonal compartment and the central domain of sensory growth cones during axonal extension, where it colocalises with microtubules. Following exposure to Sema3A, PTEN accumulates rapidly at the growth cone membrane suggesting a mechanism by which PTEN couples Sema3A signalling to growth cone collapse. These findings demonstrate a dependency on PTEN to regulate GSK-3 signalling in response to Sema3A and highlight the importance of subcellular distributions of PTEN to control growth cone behaviour.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fb8387aa81dca6cdc9bbbf3d386b12a5Test
https://doi.org/10.1242/jcs.02801Test

المؤلفون: Tobias Alther, Esther T. Stoeckli, Elena Domanitskaya

المساهمون: University of Zurich, Stoeckli, Esther T

المصدر: Development

مصطلحات موضوعية: 0301 basic medicine, Frizzled, Growth Cones, Receptors, Cell Surface, Biology, Avian Proteins, 1309 Developmental Biology, 03 medical and health sciences, 0302 clinical medicine, ROBO1, Chlorocebus aethiops, medicine, 1312 Molecular Biology, Calsyntenin, Animals, Gene Silencing, Axon, Growth cone, Molecular Biology, Floor plate, Guanine Nucleotide Dissociation Inhibitors, 030304 developmental biology, 0303 health sciences, Calcium-Binding Proteins, Wnt signaling pathway, Anatomy, Cell Biology, Axons, 10124 Institute of Molecular Life Sciences, Protein Transport, 030104 developmental biology, medicine.anatomical_structure, Phenotype, COS Cells, 570 Life sciences, biology, Axon guidance, Neuroscience, Chickens, 030217 neurology & neurosurgery, Developmental Biology

الوصف: Axon guidance at choice points depends on the precise regulation of guidance receptors on the growth cone surface. Upon arrival at the intermediate target or choice point, a switch from attraction to repulsion is required for the axon to move on. Dorsal commissural (dI1) axons crossing the ventral midline of the spinal cord in the floor plate represent a convenient model for the analysis of the molecular mechanism underlying the switch in axonal behavior. We identified a role of Calsyntenin1 in the regulation of vesicular trafficking of guidance receptors in dI1 axons at choice points. In cooperation with RabGDI, Calsyntenin1 shuttles Rab11-positive vesicles containing Robo1 to the growth cone surface in a precisely regulated manner. In contrast, Calsyntenin1-mediated trafficking of Frizzled3, a guidance receptor in the Wnt pathway, is independent of RabGDI. Thus, tightly regulated insertion of guidance receptors, which is required for midline crossing and the subsequent turn into the longitudinal axis, is achieved by specific trafficking.

وصف الملف: 528.pdf - application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dca5fde0bb139c632247e38cb4b4bef6Test
https://doi.org/10.1242/jcs.189274Test

المؤلفون: Estuardo Robles, Timothy M. Gomez, Jonathan P. Myers, Allison Ducharme-Smith

المصدر: Journal of Cell Science.

مصطلحات موضوعية: Growth Cones, Motility, macromolecular substances, GTPase, CDC42, Biology, Focal adhesion, Xenopus laevis, Cell Movement, Animals, Humans, cdc42 GTP-Binding Protein, Growth cone, Molecular Biology, Brain-Derived Neurotrophic Factor, Cell Biology, Axons, Cell biology, Cdc42 GTP-Binding Protein, Focal Adhesion Protein-Tyrosine Kinases, Axon guidance, Laminin, sense organs, biological phenomena, cell phenomena, and immunity, Lamellipodium, Filopodia, Developmental Biology, Signal Transduction, Research Article

الوصف: There is biochemical, imaging and functional evidence that Rho GTPase signaling is a critical regulator of actin based structures such as lamellipodia and filopodia. However, while Rho GTPases are believed to serve similar functions in growth cones, the spatiotemporal dynamics of Rho GTPase signaling has not been examined in living growth cones in response to known axon guidance cues. Here we provide the first measurements of Cdc42 activity in living growth cones acutely stimulated with both growth promoting and inhibiting axon guidance cues. Interestingly, we find that both permissive and repulsive factors can work by modulating Cdc42 activity, but in opposite directions. We find that the growth promoting factors laminin and BDNF activate Cdc42 while the inhibitor Slit2 reduces Cdc42 activity in growth cones. Remarkably, we find that regulation of focal adhesion kinase (FAK) activity is a common upstream modulator of Cdc42 by BDNF, laminin, and Slit. These findings suggest that rapid modulation of Cdc42 signaling through FAK by receptor activation underlies changes in growth cone motility in response to permissive and repulsive guidance cues.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::78ba119421228c7d3579142fbde8e724Test
https://doi.org/10.1242/jcs.100107Test

المؤلفون: Kelly A. Gregus, Robert H. Nichol, Miguel Santiago-Medina, Timothy M. Gomez, Sean M. O'Toole

المصدر: Journal of Cell Science. 128:e1-e1

مصطلحات موضوعية: Podosome, Growth Cones, Immunoblotting, Matrix (biology), Biology, Extracellular matrix, Xenopus laevis, Imaging, Three-Dimensional, Microtubule, Animals, Humans, Growth cone, Molecular Biology, Research Articles, Actin, Motor Neurons, Reverse Transcriptase Polymerase Chain Reaction, Cell Biology, Immunohistochemistry, Actins, Axons, Matrix Metalloproteinases, Extracellular Matrix, Cell biology, Adaptor Proteins, Vesicular Transport, Invadopodia, Axon guidance, Cell Surface Extensions, Neural development, Developmental Biology

الوصف: Invadopodia and podosomes, collectively referred to as invadosomes, are F-actin-rich basal protrusions of cells that provide sites of attachment to and degradation of the extracellular matrix. Invadosomes promote the invasion of cells, ranging from metastatic cancer cells to immune cells, into tissue. Here, we show that neuronal growth cones form protrusions that share molecular, structural and functional characteristics of invadosomes. Growth cones from all neuron types and species examined, including a variety of human neurons, form invadosomes both in vitro and in vivo. Growth cone invadosomes contain dynamic F-actin and several actin regulatory proteins, as well as Tks5 and matrix metalloproteinases, which locally degrade the matrix. When viewed using three-dimensional super-resolution microscopy, F-actin foci often extended together with microtubules within orthogonal protrusions emanating from the growth cone central domain. Finally, inhibiting the function of Tks5 both reduced matrix degradation in vitro and disrupted motoneuron axons from exiting the spinal cord and extending into the periphery. Taken together, our results suggest that growth cones use invadosomes to target protease activity during axon guidance through tissues.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b19ce9cb741c81fea36f7dfffab7eb6cTest
https://doi.org/10.1242/jcs.169201Test

المؤلفون: Gianluca Gallo

المصدر: Journal of cell science. 119(Pt 16)

مصطلحات موضوعية: animal structures, Growth Cones, macromolecular substances, Chick Embryo, Biology, Protein Serine-Threonine Kinases, Article, Semaphorin, Ganglia, Spinal, Myosin, medicine, Animals, Pseudopodia, Axon, Growth cone, Cells, Cultured, Cytoskeleton, Myosin Type II, Neurons, rho-Associated Kinases, Intracellular Signaling Peptides and Proteins, Semaphorin-3A, Cell Biology, Actin cytoskeleton, Actins, Axons, Cell biology, Actin Cytoskeleton, medicine.anatomical_structure, nervous system, Axon guidance, sense organs, Filopodia, Chickens

الوصف: Axon guidance is mediated by the effects of attractant and repellent guidance cues on the cytoskeleton of growth cones and axons. During development, axon retraction is an important aspect of the pruning of inappropriately targeted axons in response to repellent guidance cues. I investigated the roles of RhoA-kinase and myosin II in semaphorin-3A-induced growth cone collapse and axon retraction. I report that semaphorin 3A activates myosin II in growth cones and axons. Myosin II activity is required for axon retraction but not growth cone collapse. Furthermore, semaphorin 3A promotes the formation of intra-axonal F-actin bundles in concert with the loss of F-actin in growth cone lamellipodia and filopodia. Formation of axonal F-actin bundles was independent of myosin II, but partially required RhoA-kinase activity. Conversely, RhoA-kinase activity was required to shut down F-actin polymerization underlying protrusive activity. Collectively, these observations suggest that guidance cues cause axon retraction through the coordinated activation of myosin II and the formation of intra-axonal F-actin bundles for myosin-II-based force generation. I suggest that in the context of semaphorin 3A signaling, RhoA-kinase serves as a switch to change the function of the F-actin cytoskeleton from promoting protrusive activity to generating contractile forces.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8d7b74d69054e078e0436dd5ced69d80Test
https://pubmed.ncbi.nlm.nih.gov/16899819Test

المؤلفون: Véronique Corset, Valérie Castellani, Patrick Mehlen, Nathalie Cahuzac, Anne-Odile Hueber, Zoltán Hérincs, Céline Furne

المصدر: Journal of cell science. 118(Pt 8)

مصطلحات موضوعية: Deleted in Colorectal Cancer, Growth Cones, Palmitic Acid, Receptors, Cell Surface, Cell Communication, Biology, Cell Line, Membrane Lipids, Membrane Microdomains, Palmitoylation, Netrin, medicine, Animals, Humans, Nerve Growth Factors, Axon, Growth cone, Extracellular Signal-Regulated MAP Kinases, Lipid raft, Cells, Cultured, Chemotaxis, Tumor Suppressor Proteins, fungi, Cell Biology, Raft, Netrin-1, DCC Receptor, Cell biology, Rats, Enzyme Activation, medicine.anatomical_structure, nervous system, Spinal Cord, lipids (amino acids, peptides, and proteins), Axon guidance, Cues, Cell Adhesion Molecules, Signal Transduction

الوصف: During development, axons migrate long distances in responses to attractive or repulsive signals that are detected by their growth cones. One of these signals is mediated by netrin-1, a diffusible laminin-related molecule that both attracts and repels growth cones via interaction with its receptor DCC (deleted in colorectal cancer). Here we show that DCC in both commissural neurons and immortalized cells, is partially associated with cholesterol- and sphingolipid-enriched membrane domains named lipid rafts. This localization of DCC in lipid rafts is mediated by the palmitoylation within its transmembrane region. Moreover, this raft localization of DCC is required for netrin-1-induced DCC-dependent ERK activation, and netrin-1-mediated axon outgrowth requires lipid raft integrity. Thus, the presence of axon guidance-related receptors in lipid rafts appears to be a crucial pre-requisite for growth cone response to chemo-attractive or repulsive cues.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7edaf9c5dcc4ec6ca788a4741575b881Test
https://pubmed.ncbi.nlm.nih.gov/15811950Test