Phospholipase D and phosphatidylinositol-4-phosphate 5-kinase 1 are involved in the regulation of oligodendrocyte morphological differentiation

Exp Cell Res. 2021 May 24:112654. doi: 10.1016/j.yexcr.2021.112654. Online ahead of print.ABSTRACTOligodendroglial cells (oligodendrocytes) differentiate to form the myelin that wraps neuronal axons in the central nervous system (CNS). This myelin sheath supports the propagation of saltatory conduction and protects axons from physical stresses. When oligodendrocytes do not normally differentiate to myelinate axons, their key functions as oligodendrocytes in the CNS are severely impaired. The molecular mechanics that control differentiation still remain to be clarified. Arf6 belongs to the small GTPase family and is known to be a positive regulator of oligodendrocyte differentiation. Here, we show that the phospholipase D (PLD) and phosphatidylinositol-4-phosphate 5-kinase 1 (PIP5K1) molecules, the major effectors of Arf6, are involved in the regulation of oligodendrocyte differentiation. Knockdown of PLD1 or PIP5K type 1γ (PIP5K1C) by their respective specific siRNAs in mouse oligodendroglial FBD-102b cells inhibited morphological differentiation into structures bearing myelin-like processes; this finding is consistent with the concurrent changes in expression of differentiation and myelin marker proteins. Treatment with VU0155069 or UNC3230, specific inhibitors of PLD and PIP5K1, respectively, blunted morphological differentiation and decreased expression of myelin and differentiation marker proteins. Similar results have been obtained in studies using primary oligodendrocy...

Source: Experimental Cell Research - May 27, 2021 Category: Cytology Authors: Yukino Kato Arisa Ochiai Yoichi Seki Takako Morimoto Hiroaki Oizumi Katsuya Ohbuchi Kazushige Mizoguchi Masahiro Yamamoto Hiroyuki Sakagami Yuki Miyamoto Junji Yamauchi Source Type: research