WNK1 is involved in Nogo66 inhibition of OPC differentiation.
LINGO-1 is a transmembrane receptor expressed primarily in the central nervous system (CNS) and plays an important role in myelination. Recent studies have indicated that it is also involved in oligodendrocyte precursor cell (OPC) survival and differentiation; however, the downstream signaling pathway underlying OPC development is unknown. In our previous study, we found that LINGO-1 is associated with WNK1 in mediating Nogo-induced neurite extension inhibition by RhoA activation. In an effort to identify the role of LINGO-1-WNK1 in OPCs, we first confirmed that WNK1 is also expressed in OPCs and co-localized with LINGO-1, which suppresses WNK1 expression by RNA interference-attenuated Nogo66-induced inhibition of OPC differentiation. Furthermore, we mapped the WNK1 kinase domain using several fragmented peptides to identify the key region of interaction with LINGO-1. We found that a sequence corresponding to the D6 peptide is necessary for the interaction. Finally, we found that using the TAT-D6 peptide to introduce D6 peptide into primary cultured OPC inhibits the association between LINGO-1 and WNK1 and significantly attenuates Nogo66-induced inhibition of OPC differentiation. Taken together, our results show that WNK1, via a specific region on WNK1 kinase domain, interacts with LINGO-1, thus mediating Nogo66-inhibited OPC differentiation.
Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China.
Zhao-Huan
ZH
Zhang
School of Life Sciences, Shanghai University, Shanghai 200444, China.
Jiao-Jiao
JJ
Li
School of Life Sciences, Shanghai University, Shanghai 200444, China.
Qing-Jin
QJ
Wang
School of Life Sciences, Shanghai University, Shanghai 200444, China.
Wei-Qian
WQ
Zhao
School of Life Sciences, Shanghai University, Shanghai 200444, China.
Jiang
J
Hong
Key Laboratory of Exercise and Health Sciences, Ministry of Education, Shanghai University of Sport, Shanghai 200438, China. Electronic address: xxhxxh@shu.edu.cn.
Shu-jie
SJ
Lou
School of Life Sciences, Shanghai University, Shanghai 200444, China.
Xiao-Hui
XH
Xu
D000818:Animals; D001665:Binding Sites; D002478:Cells, Cultured; D008565:Membrane Proteins / Q000378:metabolism; D015778:Minor Histocompatibility Antigens; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D055495:Neurogenesis; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000076204:WNK Lysine-Deficient Protein Kinase 1
C525164:LINGO1 protein, rat; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat; D017346:Protein Serine-Threonine Kinases; D000076204:WNK Lysine-Deficient Protein Kinase 1; C410410:Wnk1 protein, rat
Differentiation; Inhibition; LINGO-1; Oligodendrocyte; WNK1