Epithelial–mesenchymal transition, IP3 receptors and ER–PM junctions: translocation of Ca2+ signalling complexes and regulation of migration

Biochemical Journal

Tony Parker¹  Emmanuel Okeke¹  Muhammad Awais¹  Lee Haynes¹  Svetlana Voronina¹  Robert Sutton¹  Daniel Metcalf¹  Matthew Concannon¹  Malcolm Begg¹  Alexei V. Tepikin¹  Alex E. Knight¹  Hayley Dingsdale¹  Jordi Molgó¹ 

DOI  :  10.1042/BJ20150364

来源: Portland Press Limited

【 摘 要 】

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 Ca²⁺ signalling complexes in this region. Importantly, migration of PDAC cells was strongly suppressed by selective inhibition of IP₃Rs and store-operated Ca²⁺ entry (SOCE), indicating that these mechanisms are functionally required for migration.

【 授权许可】

Unknown