Role of Unc51.1 and Its Binding Partners in CNS Axon Outgrowth

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2004 Mar 12

PMID 15014045

Citations 94

Authors

Toshifumi Tomoda

Jee Hae Kim

Caixin Zhan

Mary E Hatten

Affiliations

Soon will be listed here.

Abstract

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.

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