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Epithelial-mesenchymal transition, IP3 receptors and ER-PM junctions:
translocation of Ca2+ signalling complexes and regulation of migration
#MMPMID26759379
Okeke E
; Parker T
; Dingsdale H
; Concannon M
; Awais M
; Voronina S
; Molgó J
; Begg M
; Metcalf D
; Knight AE
; Sutton R
; Haynes L
; Tepikin AV
Biochem J
2016[Mar]; 473
(6
): 757-67
PMID26759379
show ga
Disconnection of a cell from its epithelial neighbours and the formation of a
mesenchymal phenotype are associated with profound changes in the distribution of
cellular components and the formation of new cellular polarity. We observed a
dramatic redistribution of inositol trisphosphate receptors (IP3Rs) and stromal
interaction molecule 1 (STIM1)-competent endoplasmic reticulum-plasma membrane
junctions (ER-PM junctions) when pancreatic ductal adenocarcinoma (PDAC) cells
disconnect from their neighbours and undergo individual migration. In cellular
monolayers IP3Rs are juxtaposed with tight junctions. When individual cells
migrate away from their neighbours IP3Rs preferentially accumulate at the leading
edge where they surround focal adhesions. Uncaging of inositol trisphosphate
(IP3) resulted in prominent accumulation of paxillin in focal adhesions,
highlighting important functional implications of the observed novel structural
relationships. ER-PM junctions and STIM1 proteins also migrate to the leading
edge and position closely behind the IP3Rs, creating a stratified distribution of
Ca(2+) signalling complexes in this region. Importantly, migration of PDAC cells
was strongly suppressed by selective inhibition of IP3Rs and store-operated
Ca(2+) entry (SOCE), indicating that these mechanisms are functionally required
for migration.
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