Cross-talk between the mechano-gated K2P channel TREK-1 and the actin cytoskeleton.
TREK-1 (KCNK2) is a K(2P) channel that is highly expressed in fetal neurons. This K(+) channel is opened by a variety of stimuli, including membrane stretch and cellular lipids. Here, we show that the expression of TREK-1 markedly alters the cytoskeletal network and induces the formation of actin- and ezrin-rich membrane protrusions. The genetic inactivation of TREK-1 significantly alters the growth cone morphology of cultured embryonic striatal neurons. Cytoskeleton remodelling is crucially dependent on the protein kinase A phosphorylation site S333 and the interactive proton sensor E306, but is independent of channel permeation. Conversely, the actin cytoskeleton tonically represses TREK-1 mechano-sensitivity. Thus, the dialogue between TREK-1 and the actin cytoskeleton might influence both synaptogenesis and neuronal electrogenesis.
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UMR 6097, Université de Nice-Sophia Antipolis, Institut Paul Hamel, 660 Route des Lucioles, 06560 Valbonne, France.
Inger
I
Lauritzen
Jean
J
Chemin
Eric
E
Honoré
Martine
M
Jodar
Nicolas
N
Guy
Michel
M
Lazdunski
Amanda
A
Jane Patel
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D020868:Gene Silencing; D015640:Ion Channel Gating; D040542:Mechanotransduction, Cellular; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D024683:Potassium Channels, Tandem Pore Domain / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011554:Pseudopodia / Q000378:metabolism; D014162:Transfection; D000099149:Ezrin
D000199:Actins; D017868:Cyclic AMP-Dependent Protein Kinases; D003598:Cytoskeletal Proteins; D010750:Phosphoproteins; D024683:Potassium Channels, Tandem Pore Domain; D000099149:Ezrin; C103742:potassium channel protein TREK-1