hGAAP promotes cell adhesion and migration via the stimulation of store-operated Ca2+ entry and calpain 2.
Golgi antiapoptotic proteins (GAAPs) are highly conserved Golgi membrane proteins that inhibit apoptosis and promote Ca(2+) release from intracellular stores. Given the role of Ca(2+) in controlling cell adhesion and motility, we hypothesized that human GAAP (hGAAP) might influence these events. In this paper, we present evidence that hGAAP increased cell adhesion, spreading, and migration in a manner that depended on the C-terminal domain of hGAAP. We show that hGAAP increased store-operated Ca(2+) entry and thereby the activity of calpain at newly forming protrusions. These hGAAP-dependent effects regulated focal adhesion dynamics and cell migration. Indeed, inhibition or knockdown of calpain 2 abrogated the effects of hGAAP on cell spreading and migration. Our data reveal that hGAAP is a novel regulator of focal adhesion dynamics, cell adhesion, and migration by controlling localized Ca(2+)-dependent activation of calpain.
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, England, UK.
Nuno
N
Saraiva
David L
DL
Prole
Guia
G
Carrara
Benjamin F
BF
Johnson
Colin W
CW
Taylor
Maddy
M
Parsons
Geoffrey L
GL
Smith
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002154:Calpain / Q000378:metabolism*; D002448:Cell Adhesion; D002465:Cell Movement; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*
D008565:Membrane Proteins; C518281:TMBIM4 protein, human; D002154:Calpain; C569870:CAPN2 protein, human; D002118:Calcium