title: The N-terminal domain of the type 1 Ins(1,4,5)P3 receptor stably expressed in MDCK cells interacts with myosin IIA and alters epithelial cell morphology.
abstract: Cytosolic Ca(2+) controls a wide range of cellular events. The versatility of this second messenger depends on its ability to form diverse spatial and temporal patterns, including waves and oscillations. Ca(2+)-signaling patterns are thought to be determined in part by the subcellular distribution of inositol (1,4,5)-trisphosphate receptors [Ins(1,4,5)P(3)Rs] but little is currently known about how the localization of the Ins(1,4,5)P(3)R itself is regulated. Here, we report that the recruitment of GFP-tagged Ins(1,4,5)P(3)Rs in the vicinity of tight junctions in Madin-Darby canine kidney (MDCK) cells requires the N-terminal domain. Stable expression of this domain in polarized MDCK cells induced a flattened morphology, affected cytokinesis, accelerated cell migration in response to monolayer wounding and interfered with the cortical targeting of myosin IIA. In addition, downregulation of myosin IIA in polarized MDCK cells was found to mimic the effects of stable expression of the N-terminal part of Ins(1,4,5)P(3)R on cell shape and to alter localization of endogenous Ins(1,4,5)P(3)Rs. Taken together, these results support a model in which the recruitment of Ins(1,4,5)P(3)Rs at the apex of the lateral membrane in polarized MDCK cells, involves myosin IIA and might be important for the regulation of cortical actin dynamics.
authors.affiliation: CNRS UMR 8080, 91405 Orsay, France.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Hours
authors.forename: Laurence
authors.initials: L
authors.lastname: Mery
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002452:Cell Count; D002453:Cell Cycle; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D048430:Cell Shape; D004285:Dogs; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000737:chemistry* / Q000378:metabolism*; D051379:Mice; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D019108:Tight Junctions / Q000378:metabolism
chemical_list: D000199:Actins; D053496:Inositol 1,4,5-Trisphosphate Receptors; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D024507:Nonmuscle Myosin Type IIA