Formation of Kv2.1-FAK complex as a mechanism of FAK activation, cell polarization and enhanced motility.
Focal adhesion kinase (FAK) plays key roles in cell adhesion and migration. We now report that the delayed rectifier Kv2.1 potassium channel, through its LD-like motif in N-terminus, may interact with FAK and enhance phosphorylation of FAK(397) and FAK(576/577). Overlapping distribution of Kv2.1 and FAK was observed on soma and proximal dendrites of cortical neurons. FAK expression promotes a polarized membrane distribution of the Kv2.1 channel. In Kv2.1-transfected CHO cells, formation of the Kv2.1-FAK complex was stimulated by fibronectin/integrin and inhibited by the K(+) channel blocker tetraethylammonium (TEA). FAK phosphorylation was minimized by shRNA knockdown of the Kv2.1 channel, point mutations of the N-terminus, and TEA, respectively. Cell migration morphology was altered by Kv2.1 knockdown or TEA, hindering cell migration activity. In wound healing tests in vitro and a traumatic injury animal model, Kv2.1 expression and co-localization of Kv2.1 and FAK significantly enhanced directional cell migration and wound closure. It is suggested that the Kv2.1 channel may function as a promoting signal for FAK activation and cell motility.
Wei
Jian-Feng
JF
Key Laboratory of Combined Multi-organ Transplantation of Ministry of Health China, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Wei
Ling
L
Zhou
Xin
X
Lu
Zhong-Yang
ZY
Francis
Kevin
K
Hu
Xin-Yang
XY
Liu
Yu
Y
Xiong
Wen-Cheng
WC
Zhang
Xiao
X
Banik
Naren L
NL
Zheng
Shu-Sen
SS
Yu
Shan Ping
SP
D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion; D002462:Cell Membrane / Q000201:enzymology; D002465:Cell Movement / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D048430:Cell Shape; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D003315:Cornea / Q000503:physiopathology; D065306:Corneal Injuries; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D017354:Point Mutation; D026902:Potassium Channel Blockers / Q000494:pharmacology; D025941:Protein Interaction Mapping; D011554:Pseudopodia / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D051669:Shab Potassium Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019789:Tetraethylammonium / Q000494:pharmacology; D014162:Transfection; D014945:Wound Healing
D005353:Fibronectins; D016023:Integrins; C496990:Kcnb1 protein, mouse; D046912:Multiprotein Complexes; D026902:Potassium Channel Blockers; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D051669:Shab Potassium Channels; D019789:Tetraethylammonium; D051417:Focal Adhesion Kinase 1; C496051:Ptk2 protein, mouse