CaMKK2 Regulates Mechanosensitive Assembly of Contractile Actin Stress Fibers

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Tojkander , S , Ciuba , K & Lappalainen , P 2018 , ' CaMKK2 Regulates Mechanosensitive Assembly of Contractile Actin Stress Fibers ' , Cell Reports , vol. 24 , no. 1 , pp. 11-19 . https://doi.org/10.1016/j.celrep.2018.06.011

Title: CaMKK2 Regulates Mechanosensitive Assembly of Contractile Actin Stress Fibers
Author: Tojkander, Sari; Ciuba, Katarzyna; Lappalainen, Pekka
Contributor: University of Helsinki, Soluvälitteiset voimat syöpäsolujen invaasiossa
University of Helsinki, Institute of Biotechnology
University of Helsinki, Institute of Biotechnology
Date: 2018-07-03
Language: eng
Number of pages: 9
Belongs to series: Cell Reports
ISSN: 2211-1247
URI: http://hdl.handle.net/10138/239803
Abstract: Stress fibers are contractile actomyosin bundles that guide cell adhesion, migration, and morphogenesis. Their assembly and alignment are under precise mechanosensitive control. Thus, stress fiber networks undergo rapid modification in response to changes in biophysical properties of the cell's surroundings. Stress fiber maturation requires mechanosensitive activation of 5 0 AMP-activated protein kinase (AMPK), which phosphorylates vasodilator- stimulated phosphoprotein (VASP) to inhibit actin polymerization at focal adhesions. Here, we identify Ca2+-calmodulin-dependent kinase kinase 2 (CaMKK2) as a critical upstream factor controlling mechanosensitive AMPK activation. CaMKK2 and Ca2+ influxes were enriched around focal adhesions at the ends of contractile stress fibers. Inhibition of either CaMKK2 or mechanosensitive Ca2+ channels led to defects in phosphorylation of AMPK and VASP, resulting in a loss of contractile bundles and a decrease in cell-exerted forces. These data provide evidence that Ca2+, CaMKK2, AMPK, and VASP form a mechanosensitive signaling cascade at focal adhesions that is critical for stress fiber assembly.
Subject: 1182 Biochemistry, cell and molecular biology
413 Veterinary science
AMPK
FORCE
LKB1
MECHANOTRANSDUCTION
MIGRATING CELLS
PHOSPHORYLATION
PROTEIN-KINASE KINASE
SKELETAL-MUSCLE
TRP CHANNELS
UPSTREAM
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