Role of Unc51.1 and its binding partners in CNS axon outgrowth.
Previous studies showed that the serine/threonine kinase Unc51.1 is one of the earliest genes in neuronal differentiation and is required for granule cell axon formation. To examine the mechanism of Unc51.1 regulation of axon extension, we have identified two direct binding partners. The first, SynGAP, a negative regulator of Ras, is expressed within axons and growth cones of developing granule cells. Overexpression of SynGAP blocks neurite outgrowth by a mechanism that involves Ras-like GTPase cascade. The second binding partner is a PDZ domain-containing scaffolding protein, Syntenin, that binds Rab5 GTPase, the activity of which is attenuated by SynGAP. Thus, our results demonstrate that the Unc51.1-containing protein complex governs axon formation via Ras-like GTPase signaling and through regulation of the Rab5-mediated endocytic pathways within developing axons.
Tomoda
Toshifumi
T
Laboratory of Developmental Neurobiology, The Rockefeller University, New York, New York 10021-6399, USA.
Kim
Jee Hae
JH
Zhan
Caixin
C
Hatten
Mary E
ME
D000818:Animals; D000071189:Autophagy-Related Protein-1 Homolog; D001369:Axons / Q000201:enzymology* / Q000648:ultrastructure; D002352:Carrier Proteins / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation; D002490:Central Nervous System / Q000196:embryology / Q000254:growth & development*; D005314:Embryonic and Fetal Development / Q000502:physiology; D004705:Endocytosis; D020690:GTPase-Activating Proteins / Q000378:metabolism / Q000502:physiology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000201:enzymology / Q000648:ultrastructure; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D053676:Syntenins; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000378:metabolism / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism
D002352:Carrier Proteins; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; C484513:Sdcbp protein, mouse; C484512:Syngap1 protein, mouse; D053676:Syntenins; D020703:ras GTPase-Activating Proteins; C401061:Ulk2 protein, mouse; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases; C112444:Ulk1 protein, mouse; D020696:rab5 GTP-Binding Proteins; D018631:ras Proteins