Ephrin-B3 reverse signaling through Grb4 and cytoskeletal regulators mediates axon pruning
| العنوان: | Ephrin-B3 reverse signaling through Grb4 and cytoskeletal regulators mediates axon pruning |
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| المؤلفون: | Mark Henkemeyer, Nan-Jie Xu |
| المصدر: | Nature neuroscience |
| بيانات النشر: | Springer Science and Business Media LLC, 2009. |
| سنة النشر: | 2009 |
| مصطلحات موضوعية: | Dock180, hippocampus, Growth Cones, Ephrin-B3, Mice, Transgenic, macromolecular substances, Biology, Article, Mice, 03 medical and health sciences, 0302 clinical medicine, Axon terminal, Transduction, Genetic, mossy fiber, Chlorocebus aethiops, medicine, Animals, NCK2, Ephrin, Gene Knock-In Techniques, Ephrin B3, Axon, Cells, Cultured, reverse signaling, Adaptor Proteins, Signal Transducing, 030304 developmental biology, Hippocampal mossy fiber, Mice, Knockout, Oncogene Proteins, 0303 health sciences, axon guidance, General Neuroscience, tyrosine phosphorylation, Actins, Axons, Coculture Techniques, Cell biology, Cytoskeletal Proteins, medicine.anatomical_structure, nervous system, COS Cells, Mossy Fibers, Hippocampal, Axon guidance, Neuroscience, 030217 neurology & neurosurgery, Signal Transduction |
| الوصف: | It has been suggested that ephrin-B proteins have receptor-like roles in the control of axon pathfinding by repulsion, although it is largely unknown how the reverse signals are coupled to downstream intracellular molecules and how they induce cytoskeletal reorganization at the axon terminal. We found that ephrin-B3 (EB3) was able to function as a repulsive guidance receptor and mediate stereotyped pruning of murine hippocampal mossy fiber axons during postnatal development. Targeted intracellular point mutants showed that axon pruning requires tyrosine phosphorylation-dependent reverse signaling and coupling to the SH2/SH3 adaptor protein Grb4 (also known as Nckbeta/Nck2). Furthermore, we found that the second SH3 domain of Grb4 is required and sufficient for axon pruning/retraction by mediating interactions with Dock180 and PAK to bring about guanine nucleotide exchange and signaling downstream of Rac, respectively. Our results reveal a previously unknown pathway that controls axon pruning and elucidate the biochemical mechanism by which ephrin-B reverse signals regulate actin dynamics to bring about the retraction of growth cones. |
| تدمد: | 1546-1726 1097-6256 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a2086d8ffcba5ffbebe3372767d74eedTest https://doi.org/10.1038/nn.2254Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a2086d8ffcba5ffbebe3372767d74eed |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461726 10976256 |
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