Defining the PIPKIgamma707/SNX5 interaction and its possible association with E-cadherin

[摘要] E-cadherin, a cell adhesion molecule and tumor suppressor plays an important role in suppressing metastasis of cancers of epithelial origin by acting as the cornerstone of adherens junctions, which facilitate adhesion between epithelial cells. The type I gamma phosphatidylinositol phosphate kinases (PIPKIgamma) directly bind E-cadherin and produce phosphatidylinositol 4,5-bisphosphate (PI4,5P2), a lipid messenger whose localized generation is necessary for E-cadherin transport and AJ formation. The sorting nexins are a family of proteins that bind multiple phosphoinositides and function in endocytic and endosomal trafficking pathways via vesicles which internalize extracellular components. We have identified a novel splice variant, PIPKIgamma707 that associates with both E-cadherin and sorting nexin 5 (SNX5) independently in vivo. Data presented here demonstrate that amino acids 645- 651 of PIPKI?707;;s C-terminus are largely responsible for mediating the interaction between Igamma707 and sorting nexin 5. Results also indicate the possible existence of a PIPKIgamma707/SNX5/ECD complex within epithelial cells, suggesting that PIPKIgamma707 and SNX5 may play a role in the proper trafficking of E-cadherin.

[发布机构] University of Wisconsin

[效力级别] Biochemistry

[关键词] Pharmacology;Biochemistry