Physiological functions of the small GTPase Arf6 in the nervous system.
The small GTPase ADP-ribosylation factor 6 (Arf6) plays important roles in membrane dynamics-based neuronal cell events such as neurite outgrowth and spine formation. However, physiological functions of Arf6 in the nervous system at whole animal level have not yet been explored. We have recently generated conditional knockout mice lacking Arf6 in neurons or oligodendrocytes of central nervous system (CNS) or both cell lineages, and analyzed them. We found that ablation of Arf6 gene from neurons, but not from oligodendrocytes, caused the defect in axon myelination at the fimbria of hippocampus (Fim) and corpus callosum (CC). We also found that migration of oligodendrocyte precursor cells (OPCs) from the subventricular zone to the Fim and CC in mice lacking Arf6 in neurons was impaired. Finally, it was found that secretion of fibroblast growth factor-2 (FGF-2), a guidance factor for OPC migration, from hippocampi lacking Arf6 was impaired. Collectively, these findings demonstrate that Arf6 in neurons of the CNS plays an important role in OPC migration by regulating secretion of FGF-2 from neurons, thereby contributing to the axon myelination. Here, we discuss our current understanding of physiological functions of Arf6 in the nervous system.
a Faculty of Medicine and Graduate School of Comprehensive Human Sciences; Department of Physiological Chemistry ; University of Tsukuba ; Tennodai, Tsukuba , Japan.
Masahiro
M
Akiyama
Yasunori
Y
Kanaho
D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism; D009420:Nervous System / Q000166:cytology* / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000502:physiology
D000089982:ADP-Ribosylation Factor 6; D016222:Fibroblast Growth Factor 2; D020727:ADP-Ribosylation Factors; C000715348:ARF6 protein, human; C000715727:Arf6 protein, mouse
Arf6; FGF-2; conditional knockout mice; migration; myelination; neurons; oligodendrocytes