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Myelin‐associated glycoprotein inhibits neurite outgrowth through inactivation of the small GTPase Rap1
Author(s) -
Nikulina Elena,
Gkioka Vasiliki,
Siddiq Mustafa M.,
Mellado Wilfredo,
Hilaire Melissa,
Cain Christine R.,
Hannila Sari S.,
Filbin Marie T.
Publication year - 2020
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.13740
Subject(s) - neurite , rap1 , myelin , myelin associated glycoprotein , microbiology and biotechnology , small gtpase , neurotrophin , gtpase , nerve growth factor , chemistry , biology , neuroscience , central nervous system , biochemistry , signal transduction , receptor , in vitro
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 and that this activation can be blocked by myelin‐associated glycoprotein (MAG) or central nervous system 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.