| First Author | Kamakura S | Year | 2013 |
| Journal | Dev Cell | Volume | 26 |
| Issue | 3 | Pages | 292-302 |
| PubMed ID | 23891662 | Mgi Jnum | J:359733 |
| Mgi Id | MGI:6839559 | Doi | 10.1016/j.devcel.2013.06.008 |
| Citation | Kamakura S, et al. (2013) The cell polarity protein mInsc regulates neutrophil chemotaxis via a noncanonical G protein signaling pathway. Dev Cell 26(3):292-302 |
| abstractText | Successful chemotaxis requires not only increased motility but also sustained directionality. Here, we show that, during neutrophil chemotaxis via receptors coupled with the Gi family of heterotrimeric G proteins, directional movement is regulated by mInsc, a mammalian protein distantly related to the Drosophila polarity-organizer Inscuteable. The GDP-bound, Gbetagamma-free Galphai subunit accumulates at the front of chemotaxing neutrophils to recruit mInsc-complexed with the Par3-aPKC evolutionarily conserved polarity complex-via LGN/AGS3 that simultaneously binds to Galphai-GDP and mInsc. Both mInsc-deficient and aPKC-blocked neutrophils exhibit a normal motile activity but migrate in an undirected manner. mInsc deficiency prevents neutrophils from efficiently stabilizing pseudopods at the leading edge; the stability is restored by wild-type mInsc, but not by a mutant protein defective in binding to LGN/AGS3. Thus, mInsc controls directional migration via noncanonical G protein signaling, in which Gbetagamma-free Galphai-GDP, a product from Galphai-GTP released after receptor activation, plays a central role. |
