Na/H exchanger NHE1 acts upstream of rho GTPases to promote neurite outgrowth

Journal of Cell Communication and Signaling

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