المؤلفون: Visar Ajeti, Paul Forscher, Arash Fereydooni, Enrique M. De La Cruz, Nicole Tsai, William R. Burns, Michael P. Murrell, Xiao-Feng Zhang

المصدر: The Journal of Cell Biology

مصطلحات موضوعية: Cofilin 1, Serotonin, Neurite, Neurogenesis, Growth Cones, macromolecular substances, Biology, Catalysis, Article, 03 medical and health sciences, 0302 clinical medicine, Aplysia, Myosin, Neurites, medicine, Animals, Phosphorylation, Axon, Growth cone, Protein Kinase C, Research Articles, Actin, Protein kinase C, Mechanical Phenomena, 030304 developmental biology, Myosin Type II, Neurons, 0303 health sciences, Hyperactivation, Microfilament Proteins, Cell Biology, Cofilin, Actins, Axons, Actin Cytoskeleton, medicine.anatomical_structure, Biophysics, 030217 neurology & neurosurgery

الوصف: Synergism between myosin II contractility and cofilin activity modulates serotonin-dependent axon growth. Normally, cofilin-dependent decreases in actin density are compensated by increases in point contact density and traction force; however, myosin hyperactivation leads to catastrophic decreases in actin network density and neurite retraction.
Serotonin (5-HT) is known to increase the rate of growth cone advance via cofilin-dependent increases in retrograde actin network flow and nonmuscle myosin II activity. We report that myosin II activity is regulated by PKC during 5-HT responses and that PKC activity is necessary for increases in traction force normally associated with these growth responses. 5-HT simultaneously induces cofilin-dependent decreases in actin network density and PKC-dependent increases in point contact density. These reciprocal effects facilitate increases in traction force production in domains exhibiting decreased actin network density. Interestingly, when PKC activity was up-regulated, 5-HT treatments resulted in myosin II hyperactivation accompanied by catastrophic cofilin-dependent decreases in actin filament density, sudden decreases in traction force, and neurite retraction. These results reveal a synergistic relationship between cofilin and myosin II that is spatiotemporally regulated in the growth cone via mechanocatalytic effects to modulate neurite growth.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fdd1187d8bbbc147f12fbee0c579dbefTest
https://doi.org/10.1083/jcb.201810054Test

المؤلفون: Christine Fagotto-Kaufmann, Anne Debant, Amandine Falco, Freddy Jeanneteau, Marion Bonhomme, Jérôme Boudeau, Niels Galjart, Jeffrey van Haren, Carlos Sánchez-Huertas

المساهمون: Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Department of Cell Biology and Genetics, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Agence Nationale de la Recherche (France), Fondation pour la Recherche Médicale, Centre National de la Recherche Scientifique (France), Université de Montpellier, Institut National de la Santé et de la Recherche Médicale (France), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Cell biology

المصدر: Journal of Cell Biology
Journal of Cell Biology, Rockefeller University Press, 2020, 219 (9), ⟨10.1083/jcb.201905199⟩
The Journal of Cell Biology
Digital.CSIC. Repositorio Institucional del CSIC
instname
Journal of Cell Biology, 219(9):e201905199. Rockefeller University Press

مصطلحات موضوعية: genetic structures, [SDV]Life Sciences [q-bio], Growth Cones, macromolecular substances, Biology, Microtubules, Axonal growth cone, Article, Cell Line, Mice, 03 medical and health sciences, 0302 clinical medicine, Cell Movement, Microtubule, Netrin, medicine, Animals, Humans, Axon, Growth cone, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS, Cytoskeleton, 030304 developmental biology, 0303 health sciences, Cell Biology, Netrin-1, Actins, Axons, Axon Guidance, 3. Good health, Cell biology, Actin Cytoskeleton, Crosstalk (biology), HEK293 Cells, medicine.anatomical_structure, nervous system, [SDU]Sciences of the Universe [physics], NAV1, Female, Axon guidance, sense organs, Microtubule-Associated Proteins, 030217 neurology & neurosurgery, Neuroscience, Protein Binding

الوصف: Trabajo presentado al 17th Meeting of the Spanish Society for Developmental Biology (SEBD), celebrado de forma virtual del 18 al 20 de noviembre de 2020.
The microtubule plus-end tracking proteins (+TIPs) are central players in the coordination between the microtubules (MT) and actin network in the growth cone (GC) during axon guidance. The +TIP Navigator-1 (NAV1) is expressed in the developing nervous system, yet its neuronal functions remain poorly elucidated. Here, we report that NAV1 controls the GC dynamics in cortical axons and it is required for axon turning towards a gradient of netrin-1. NAV1 accumulates in the peripheral domain of axonal GCs and is able to bind actin filaments (F-actin) and microtubules in vitro. Indeed, we found that NAV1 binds MTs independently of EB1 and crosslinks non-polymerizing MT plus-ends to actin filaments in axonal GCs. Therefore, NAV1 prevents MT depolymerization in the F-actin-rich areas by stabilizing the non-growing MT plus-ends. Our findings pinpoint NAV1 as a new key player in the actin-MT crosstalk, that promotes MT persistence within the GC periphery and controls GC steering. Additionally, we present data assigning to NAV1 a role in the radial migration of cortical projection neurons in vivo.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4b40cd71404de05e001389066c80de09Test
https://doi.org/10.1083/jcb.201905199Test

المؤلفون: Rumelo Amor, Wei Li, Jiang Anmin, Chunxia Liu, Frederic A. Meunier, Sally Martin, Merja Joensuu, Pranesh Padmanabhan, Vanessa Lanoue, Golnoosh Shamsollahi, Tong Wang, Andreas Papadopulos

المصدر: The Journal of Cell Biology

مصطلحات موضوعية: Growth Cones, macromolecular substances, Biology, Axonal Transport, Microtubules, Article, Contractility, 03 medical and health sciences, Contractile Proteins, 0302 clinical medicine, Cell Movement, medicine, Animals, Spectrin, Axon, Cytoskeleton, Actin, 030304 developmental biology, Neurons, 0303 health sciences, Trafficking, Autophagosomes, Actomyosin, Cell Biology, Actins, Axons, Rats, Actin Cytoskeleton, Protein Transport, medicine.anatomical_structure, nervous system, Biophysics, Axoplasmic transport, Axonal degeneration, 030217 neurology & neurosurgery, Neuroscience, Muscle Contraction, Initial segment, Overall efficiency

الوصف: Wang et al. find that axonal radial contractility and local expansion control the retrograde trafficking of large cargoes. The periodic actomyosin-II network comprises NM-II filaments and F-actin rings. Loss of actomyosin-II–mediated radial contractility causes defects in axonal trafficking and stability, leading to degeneration.
Most mammalian neurons have a narrow axon, which constrains the passage of large cargoes such as autophagosomes that can be larger than the axon diameter. Radial axonal expansion must therefore occur to ensure efficient axonal trafficking. In this study, we reveal that the speed of various large cargoes undergoing axonal transport is significantly slower than that of small ones and that the transit of diverse-sized cargoes causes an acute, albeit transient, axonal radial expansion, which is immediately restored by constitutive axonal contractility. Using live super-resolution microscopy, we demonstrate that actomyosin-II controls axonal radial contractility and local expansion, and that NM-II filaments associate with periodic F-actin rings via their head domains. Pharmacological inhibition of NM-II activity significantly increases axon diameter by detaching the NM-II from F-actin and impacts the trafficking speed, directionality, and overall efficiency of long-range retrograde trafficking. Consequently, prolonged NM-II inactivation leads to disruption of periodic actin rings and formation of focal axonal swellings, a hallmark of axonal degeneration.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0cf1ebebd023b41f3c5eba3c186b1f09Test
https://doi.org/10.1083/jcb.201902001Test

المؤلفون: Ning Li, Jonathan X. Chia, Tatyana Svitkina, Kristi L. Neufeld, Nadia Efimova, Christopher J. Lengner, Changsong Yang

المصدر: The Journal of Cell Biology

مصطلحات موضوعية: Adenomatous polyposis coli, Adenomatous Polyposis Coli Protein, Growth Cones, Hippocampus, Microtubules, Article, Protein filament, Rats, Sprague-Dawley, 03 medical and health sciences, Mice, 0302 clinical medicine, Microtubule, Cell Movement, Animals, Cytoskeleton, Growth cone, Actin, Cells, Cultured, 030304 developmental biology, Neurons, 0303 health sciences, biology, Migration, Motility, Cell migration, Cell Biology, Actin cytoskeleton, Actins, Cell biology, Rats, Mice, Inbred C57BL, Actin Cytoskeleton, Adenomatous Polyposis Coli, biology.protein, 030217 neurology & neurosurgery, Neuroscience

الوصف: Efimova et al. show that adenomatous polyposis coli (APC) at microtubule tips triggers assembly of a branched actin network when the microtubule hits the plasma membrane in neuronal growth cones. These findings uncover a new mechanism of microtubule-dependent cell navigation.
Cell migration is driven by pushing and pulling activities of the actin cytoskeleton, but migration directionality is largely controlled by microtubules. This function of microtubules is especially critical for neuron navigation. However, the underlying mechanisms are poorly understood. Here we show that branched actin filament networks, the main pushing machinery in cells, grow directly from microtubule tips toward the leading edge in growth cones of hippocampal neurons. Adenomatous polyposis coli (APC), a protein with both tumor suppressor and cytoskeletal functions, concentrates at the microtubule-branched network interface, whereas APC knockdown nearly eliminates branched actin in growth cones and prevents growth cone recovery after repellent-induced collapse. Conversely, encounters of dynamic APC-positive microtubule tips with the cell edge induce local actin-rich protrusions. Together, we reveal a novel mechanism of cell navigation involving APC-dependent assembly of branched actin networks on microtubule tips.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b36a670c64abda56fa972b6e32a579d3Test
https://pubmed.ncbi.nlm.nih.gov/32597939Test

المؤلفون: Stephanie Strohbuecker, Guido Serini, Donatella Valdembri, Antoneta Gavoci, Simone Bridi, Eleonora Oliani, Tegan A Otto, Gabriela Santos-Rodriguez, Michela Roccuzzo, Archana Iyer, Eloina Corradi, Cei Abreu-Goodger, Marie-Laure Baudet, Irene Dalla Costa

المصدر: The EMBO Journal

مصطلحات موضوعية: Retinal Ganglion Cells, RNA, Untranslated, Endosome, Growth Cones, Endosomes, Biology, neural circuit development, General Biochemistry, Genetics and Molecular Biology, Article, axon, non-coding RNAs, RNA localization, TUBB3, 03 medical and health sciences, Xenopus laevis, 0302 clinical medicine, Semaphorin, medicine, RNA Precursors, Compartment (development), Animals, Axon, Growth cone, Molecular Biology, 030304 developmental biology, 0303 health sciences, General Immunology and Microbiology, General Neuroscience, SEMA3A, Biological Transport, Articles, Non-coding RNA, RNA Biology, Axons, Cell biology, Mice, Inbred C57BL, MicroRNAs, medicine.anatomical_structure, non‐coding RNAs, Axon guidance, Female, 030217 neurology & neurosurgery, Neuroscience, Signal Transduction

الوصف: Various species of non‐coding RNAs (ncRNAs) are enriched in specific subcellular compartments, but the mechanisms orchestrating their localization and their local functions remain largely unknown. We investigated both aspects using the elongating retinal ganglion cell axon and its tip, the growth cone, as models. We reveal that specific endogenous precursor microRNAs (pre‐miRNAs) are actively trafficked to distal axons by hitchhiking primarily on late endosomes/lysosomes. Upon exposure to the axon guidance cue semaphorin 3A (Sema3A), pre‐miRNAs are processed specifically within axons into newly generated miRNAs, one of which, in turn, silences the basal translation of tubulin beta 3 class III (TUBB3), but not amyloid beta precursor protein (APP). At the organismal level, these mature miRNAs are required for growth cone steering and a fully functional visual system. Overall, our results uncover a novel mode of ncRNA transport from one cytosolic compartment to another within polarized cells. They also reveal that newly generated miRNAs are critical components of a ncRNA‐based signaling pathway that transduces environmental signals into the structural remodeling of subcellular compartments.
Pre‐miRNAs transported to distal axons are locally processed upon exposure to Sema3A and are required for growth cone steering and a fully functional visual system.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b31a023abf2aaf5e8b7ce0bf41b40d9Test
http://hdl.handle.net/2318/1729274Test

المؤلفون: Louis-Philippe Croteau, Tzu Jen Kao, Artur Kania

المصدر: Scientific Reports
Scientific Reports, Vol 9, Iss 1, Pp 1-17 (2019)

مصطلحات موضوعية: 0301 basic medicine, animal structures, Science, Growth Cones, Article, Cell membrane, 03 medical and health sciences, 0302 clinical medicine, Developmental biology, Netrin, medicine, Animals, Ephrin, Axon, Growth cone, Receptor, 030304 developmental biology, Motor Neurons, 0303 health sciences, Multidisciplinary, Axon and dendritic guidance, Chemistry, fungi, Membrane Proteins, Netrin-1, Ephrin-A5, Axons, Axon Guidance, Cell biology, 030104 developmental biology, medicine.anatomical_structure, nervous system, Proteolysis, embryonic structures, Medicine, Axon guidance, Ephrin A5, sense organs, Chickens, 030217 neurology & neurosurgery

الوصف: Axonal growth cones are guided by molecular cues in the extracellular environment. The mechanisms of combinatorial integration of guidance signals at the growth cone cell membrane are still being unravelled. Limb-innervating axons of vertebrate spinal lateral motor column (LMC) neurons are attracted to netrin-1 via its receptor, Neogenin, and are repelled from ephrin-A5 through its receptor EphA4. The presence of both cues elicits synergistic guidance of LMC axons, but the mechanism of this effect remains unknown. Using fluorescence immunohistochemistry, we show that ephrin-A5 increases LMC growth cone Neogenin protein levels and netrin-1 binding. This effect is enhanced by overexpressing EphA4 and is inhibited by blocking ephrin-A5-EphA4 binding. These effects have a functional consequence on LMC growth cone responses since bath addition of ephrin-A5 increases the responsiveness of LMC axons to netrin-1. Surprisingly, the overexpression of EphA4 lacking its cytoplasmic tail, also enhances Neogenin levels at the growth cone and potentiates LMC axon preference for growth on netrin-1. Since netrins and ephrins participate in a wide variety of biological processes, the enhancement of netrin-1 signalling by ephrins may have broad implications.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbdcce1d25825d5f520f4497f21fea2fTest
https://doi.org/10.1038/s41598-019-48519-0Test

المؤلفون: Aurélie Stil, Philippe Germain, Hosni Cherif, Samuel Laroche, Jean-François Bouchard, Sylvain Chemtob

المصدر: Cells
Volume 10
Issue 7
Cells, Vol 10, Iss 1640, p 1640 (2021)

مصطلحات موضوعية: Nervous system, retina, genetic structures, QH301-705.5, Growth Cones, Nervous System, Retinal ganglion, Article, Receptors, G-Protein-Coupled, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Thalamus, 3,5-DHBA, medicine, Animals, HCAR1, dLGN, Phosphorylation, Biology (General), Axon, Growth cone, Receptor, Protein Kinase C, Vision, Ocular, 030304 developmental biology, axon, lactate, 0303 health sciences, Retina, GPR81, Retinal, General Medicine, Cyclic AMP-Dependent Protein Kinases, Axons, eye diseases, Cell biology, Mice, Inbred C57BL, growth cone, medicine.anatomical_structure, retinal ganglion cells, chemistry, Lactates, sense organs, Filopodia, 030217 neurology & neurosurgery

الوصف: During the development of the retina and the nervous system, high levels of energy are required by the axons of retinal ganglion cells (RGCs) to grow towards their brain targets. This energy demand leads to an increase of glycolysis and L-lactate concentrations in the retina. L-lactate is known to be the endogenous ligand of the GPR81 receptor. However, the role of L-lactate and its receptor in the development of the nervous system has not been studied in depth. In the present study, we used immunohistochemistry to show that GPR81 is localized in different retinal layers during development, but is predominantly expressed in the RGC of the adult rodent. Treatment of retinal explants with L-lactate or the exogenous GPR81 agonist 3,5-DHBA altered RGC growth cone (GC) morphology (increasing in size and number of filopodia) and promoted RGC axon growth. These GPR81-mediated modifications of GC morphology and axon growth were mediated by protein kinases A and C, but were absent in explants from gpr81−/− transgenic mice. Living gpr81−/− mice showed a decrease in ipsilateral projections of RGCs to the dorsal lateral geniculate nucleus (dLGN). In conclusion, present results suggest that L-lactate and its receptor GPR81 play an important role in the development of the visual nervous system.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::47b75909e49fc71f729ef9fa932fcfeaTest
https://doi.org/10.3390/cells10071640Test

المؤلفون: Ferdi Ridvan Kiral, Vincent J. Dercksen, Max von Kleist, Steffen Prohaska, Heike Wolfenberg, Mehmet Neset Özel, Josephine Brummer, Marian Moldenhauer, P. Robin Hiesinger, Abhishek Kulkarni, Martin Weiser, Ilsa-Maria Daumann, Amr Hasan

المصدر: Dev Cell

مصطلحات موضوعية: Neurogenesis, Growth Cones, Biology, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, 0302 clinical medicine, Live cell imaging, medicine, Synapse formation, Animals, Drosophila Proteins, Computer Simulation, Pseudopodia, Axon, Growth cone, Molecular Biology, Analysis method, 030304 developmental biology, 0303 health sciences, Synapse assembly, GTPase-Activating Proteins, Intracellular Signaling Peptides and Proteins, Gene Expression Regulation, Developmental, Cell Biology, Phosphoproteins, Axons, medicine.anatomical_structure, Entire axon, Drosophila melanogaster, Synapses, Axon guidance, Seeding, Neuroscience, Filopodia, 030217 neurology & neurosurgery, Developmental Biology

الوصف: SummaryFollowing axon pathfinding, growth cones transition from stochastic filopodial exploration to the formation of a limited number of synapses. How the interplay of filopodia and synapse assembly ensures robust connectivity in the brain has remained a challenging problem. Here, we developed a new 4D analysis method for filopodial dynamics and a data-driven computational model of synapse formation for R7 photoreceptor axons in developing Drosophila brains. Our live data support a ‘serial synapse formation’ model, where at any time point only a single ‘synaptogenic’ filopodium suppresses the synaptic competence of other filopodia through competition for synaptic seeding factors. Loss of the synaptic seeding factors Syd-1 and Liprin-α leads to a loss of this suppression, filopodial destabilization and reduced synapse formation, which is sufficient to cause the destabilization of entire axon terminals. Our model provides a filopodial ‘winner-takes-all’ mechanism that ensures the formation of an appropriate number of synapses.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9481c4ec2fa5d1a8f71d158b81352a54Test
https://europepmc.org/articles/PMC6702111Test/

المؤلفون: Robin Scharrenberg, Michael R. Kreutz, Carlos G. Dotti, Dennis Eggert, Oliver Kobler, Durga Praveen Meka, Froylan Calderon de Anda, Sabine Windhorst, Birgit Schwanke, Sergei Klykov, Melanie Richter, Marina Mikhaylova, Theresa König, Irina Schaefer, Bing Zhao

المصدر: EMBO Reports
EMBO reports, 20(12):e47743

مصطلحات موضوعية: Somatic cell, Neurogenesis, Cell, Growth Cones, Cell Cycle Proteins, macromolecular substances, PCM‐1, microtubules, actin, PCM-1, neuronal development, centrosome, Biology, Biochemistry, Hippocampus, Microtubules, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Microtubule, Genetics, medicine, Animals, Growth cone, Molecular Biology, Actin, Cells, Cultured, 030304 developmental biology, Centrosome, 0303 health sciences, Gene knockdown, Microtubule organizing center, Articles, Actins, Cell biology, Rats, Mice, Inbred C57BL, medicine.anatomical_structure, Cell Adhesion, Polarity & Cytoskeleton, 030217 neurology & neurosurgery, Neuroscience

الوصف: The centrosome is thought to be the major neuronal microtubule‐organizing center (MTOC) in early neuronal development, producing microtubules with a radial organization. In addition, albeit in vitro, recent work showed that isolated centrosomes could serve as an actin‐organizing center, raising the possibility that neuronal development may, in addition, require a centrosome‐based actin radial organization. Here, we report, using super‐resolution microscopy and live‐cell imaging of cultured rodent neurons, F‐actin organization around the centrosome with dynamic F‐actin aster‐like structures with F‐actin fibers extending and retracting actively. Photoactivation/photoconversion experiments and molecular manipulations of F‐actin stability reveal a robust flux of somatic F‐actin toward the cell periphery. Finally, we show that somatic F‐actin intermingles with centrosomal PCM‐1 (pericentriolar material 1 protein) satellites. Knockdown of PCM‐1 and disruption of centrosomal activity not only affect F‐actin dynamics near the centrosome but also in distal growth cones. Collectively, the data show a radial F‐actin organization during early neuronal development, which might be a cellular mechanism for providing peripheral regions with a fast and continuous source of actin polymers, hence sustaining initial neuronal development.
During early neuronal development, centrosomes regulate F‐actin organization, thereby ensuring proper growth cone dynamics and neurite length.

وصف الملف: application/pdf; application/zip

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0673636db508f2d86b55ba67a614b31cTest
https://pubmed.ncbi.nlm.nih.gov/31650708Test

المؤلفون: Xiaoqin Fu, Clifford J. Woolf, Chen Wang, Homaira Nawabi, Daniel G. Taub, Alban Latremoliere, Philip R. Williams, Xuhua Wang, Stephane Belin, Bin Yu, Romain Cartoni, Judy S. Liu, Zhigang He, Judith A. Steen, Christopher V. Gabel, Junjie Zhu, Xiaosong Gu

المصدر: Neuron

مصطلحات موضوعية: Retinal Ganglion Cells, Doublecortin Protein, Cell Survival, Neuroscience(all), medicine.medical_treatment, Growth Cones, In Vitro Techniques, Protein Serine-Threonine Kinases, Biology, Microtubules, Retinal ganglion, Article, Mice, 03 medical and health sciences, Doublecortin-Like Kinases, 0302 clinical medicine, medicine, Animals, Axon, Growth cone, PI3K/AKT/mTOR pathway, 030304 developmental biology, Neurons, 0303 health sciences, Kinase, TOR Serine-Threonine Kinases, General Neuroscience, Regeneration (biology), Axotomy, Actins, Axons, Nerve Regeneration, Cell biology, Doublecortin, medicine.anatomical_structure, nervous system, Optic Nerve Injuries, biology.protein, Neuroscience, 030217 neurology & neurosurgery

الوصف: After axotomy, neuronal survival and growth cone re-formation are required for axon regeneration. We discovered that doublecortin-like kinases (DCLKs), members of the doublecortin (DCX) family expressed in the adult retinal ganglion cells (RGCs), play critical roles in both processes, through distinct mechanisms. Over-expression of DCLK2 accelerated growth cone re-formation in vitro and enhanced the initiation and elongation of axon re-growth after optic nerve injury. These effects depended on both the microtubule (MT)-binding domain and the serine-proline-rich (S/P-rich) region of DCXs in-cis in the same molecules. While the MT-binding domain is known to stabilize MT structures, we show that the S/P-rich region prevents F-actin destabilization in injured axon stumps. Additionally, while DCXs synergize with mTOR to stimulate axon regeneration, alone they can promote neuronal survival possibly through regulating the retrograde propagation of injury signals. Multifunctional DCXs thus represent potential targets for promoting both survival and regeneration of injured neurons.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::14f412a593b758f5d4d8da8fff9180f8Test
https://doi.org/10.1016/j.neuron.2015.10.005Test