Journal of Cell Communication and Signaling | |
Na/H exchanger NHE1 acts upstream of rho GTPases to promote neurite outgrowth | |
article | |
Sin, Wun Chey1  Tam, Nicola1  Moniz, David1  Lee, Connie1  Church, John1  | |
[1] Department of Cellular and Physiological Sciences, Life Sciences Institute, The University of British Columbia | |
关键词: NHE1; Rho GTPases; RhoA; Rac1; Cdc42; Neurite outgrowth; Netrin-1; | |
DOI : 10.1007/s12079-020-00556-5 | |
学科分类:分子生物学,细胞生物学和基因 | |
来源: Springer | |
【 摘 要 】
Na+/H+ exchanger NHE1, a major determinant of intracellular pH (pHi) in mammalian central neurons, promotes neurite outgrowth under both basal and netrin-1-stimulated conditions. The small GTP binding proteins and their effectors have a dominant role in netrin-1-stimulated neurite outgrowth. Since NHE1 has been shown previously to work downstream of the Rho GTPases-mediated polarized membrane protrusion in non-neuronal cells, we examined whether NHE1 has a similar relationship with Cdc42, Rac1 and RhoA in neuronal morphogenesis. Interestingly, our results suggest the possibility that NHE1 acting upstream of Rho GTPases to promote neurite outgrowth induced by netrin-1. First, we found that netrin-1-induced increases in the activities of Rho GTPases using FRET (Forster Resonance Energy Transfer) analyses in individual growth cones; furthermore, their increased activities were abolished by cariporide, a specific NHE1 inhibitor. Second, NHE1 inhibition had no effect on neurite retraction induced by L-α-Lysophosphatidic acid (LPA), a potent RhoA activator. The regulation of Rho GTPases by NHE1 was further evidenced by reduced Rac1, Cdc42 and RhoA activities in NHE1-null neurons. Taken together, our findings suggest that NHE1-dependent neuronal morphogenesis involves the activation of Rho-family of small GTPases.
【 授权许可】
CC BY
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