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Role for Rab3a in oligodendrocyte morphological differentiation
Author(s) -
Anitei Mihaela,
Cowan Ann E.,
Pfeiffer Steven E.,
Bansal Rashmi
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21870
Subject(s) - oligodendrocyte , microbiology and biotechnology , biology , myelin , cellular differentiation , progenitor , rab , myelin basic protein , progenitor cell , gene silencing , gtpase , stem cell , neuroscience , genetics , gene , central nervous system
Rab3a, a small GTPase important for exocytosis, is uniquely up‐regulated as oligodendrocytes enter terminal differentiation and initiate myelin biosynthesis. In this study, we analyze the role of this protein in oligodendrocyte morphological differentiation by using Rab3a overexpression and siRNAi‐mediated Rab3a silencing. We found that Rab3a silencing delayed mature oligodendrocyte morphological differentiation but did not interfere with lineage progression of OL progenitors; this is consistent with the high levels of Rab3a expressed by mature oligodendrocytes compared with progenitor cells. Overexpression of GTP‐bound, but not that of wild‐type, Rab3a delayed OL morphological differentiation; this suggests that expression of a GTP‐bound Rab3a mutant interferes with the normal function of endogenous Rab3a. We have also identified in oligodendrocytes two other exocytic small GTPases, Rab27B and RalA. Together, these findings indicate that Rab3a specifically stimulates morphological differentiation of mature oligodendrocytes and thus may be part of the necessary machinery for myelin membrane biogenesis. © 2008 Wiley‐Liss, Inc.