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Myelin-associated glycoprotein inhibits neurite outgrowth through inactivation of the small GTPase Rap1.

PUBLICATION: 
Journal Article
Authors: 
Nikulina E, Gkioka V, Siddiq MM, Mellado W, Hilaire M, Cain CR, Hannila SS, Filbin MT.
Year Published: 
2020
Publisher: 
FEBS Lett. 2020 Jan 27. doi: 10.1002/1873-3468.13740. [Epub ahead of print]
Identifiers: 
PMID: 31985825 | DOI: 10.1002/1873-3468.13740
Abstract on PubMed

Abstract

Rap1 is a small GTPase that has been implicated in dendritic development and plasticity. In this study, we investigated the role of Rap1 in axonal growth and its activation in response to neurotrophins and myelin-associated inhibitors. We report that Rap1 is activated by brain-derived neurotrophic factor (BDNF), and that this activation can be blocked by myelin-associated glycoprotein (MAG) or CNS myelin, which also induced increases in Rap1GAP1 levels. In addition, we demonstrate that adenoviral overexpression of Rap1 enhances neurite outgrowth in the presence of MAG and myelin, while inhibition of Rap1 activity through overexpression of Rap1GAP1 blocks neurite outgrowth. These findings suggest that Rap1GAP1 negatively regulates neurite outgrowth, making it a potential therapeutic target to promote axonal regeneration.