Polarized Dock Activity Drives Shh-Mediated Axon Guidance
| Autor: | Steves Morin, Shirin Makihara, Frédéric Charron, Patricia T. Yam, Jean-François Côté, Julien Ferent |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
animal structures Growth Cones RAC1 Mice Transgenic Nerve Tissue Proteins General Biochemistry Genetics and Molecular Biology 03 medical and health sciences DOCK medicine Animals Guanine Nucleotide Exchange Factors Hedgehog Proteins Axon Sonic hedgehog Cytoskeleton Growth cone Molecular Biology Cells Cultured Adaptor Proteins Signal Transducing Neurons biology Dock3 GTPase-Activating Proteins Gene Expression Regulation Developmental Cell Biology Embryo Mammalian Axons Cell biology Axon Guidance Cytoskeletal Proteins 030104 developmental biology medicine.anatomical_structure Spinal Cord embryonic structures biology.protein Axon guidance Carrier Proteins Developmental Biology |
| Zdroj: | Developmental cell. 46(4) |
| ISSN: | 1878-1551 |
| Popis: | Summary In the developing spinal cord, Sonic hedgehog (Shh) attracts commissural axons toward the floorplate. How Shh regulates the cytoskeletal remodeling that underlies growth cone turning is unknown. We found that Shh-mediated growth cone turning requires the activity of Docks, which are unconventional GEFs. Knockdown of Dock3 and 4, or their binding partner ELMO1 and 2, abolished commissural axon attraction by Shh in vitro. Dock3/4 and ELMO1/2 were also required for correct commissural axon guidance in vivo. Polarized Dock activity was sufficient to induce axon turning, indicating that Docks are instructive for axon guidance. Mechanistically, we show that Dock and ELMO interact with Boc, the Shh receptor, and that this interaction is reduced upon Shh stimulation. Furthermore, Shh stimulation translocates ELMO to the growth cone periphery and activates Rac1. This identifies Dock/ELMO as an effector complex of non-canonical Shh signaling and demonstrates the instructive role of GEFs in axon guidance. |
| Databáze: | OpenAIRE |
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