Role for Rab3a in oligodendrocyte morphological differentiation.
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.
Anitei
Mihaela
M
Department of Neuroscience, University of Connecticut Medical School, Farmington, Connecticut 06030-3401, USA.
Cowan
Ann E
AE
Pfeiffer
Steven E
SE
Bansal
Rashmi
R
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism; D034741:RNA, Small Interfering; D051381:Rats; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020826:rab3A GTP-Binding Protein / Q000378:metabolism*; D020725:ral GTP-Binding Proteins / Q000378:metabolism
D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; C107293:Rim protein, mammalian; D019204:GTP-Binding Proteins; C512956:Rab27b protein, rat; C492197:Rala protein, rat; D020691:rab GTP-Binding Proteins; D020826:rab3A GTP-Binding Protein; D020725:ral GTP-Binding Proteins