期刊
DEVELOPMENTAL CELL
卷 26, 期 3, 页码 292-302出版社
CELL PRESS
DOI: 10.1016/j.devcel.2013.06.008
关键词
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资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI grant [20117002]
- Japan Society for the Promotion of Science (JSPS) KAKENHI grant [24590385]
- Astellas Foundation for Research on Metabolic Disorders
- Grants-in-Aid for Scientific Research [24111007, 20117002, 24590385, 24590586, 25251015, 24111001, 21229002] Funding Source: KAKEN
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, G beta gamma-free G alpha i 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 G alpha i-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 G beta gamma-free G alpha i-GDP, a product from G alpha i-GTP released after receptor activation, plays a central role.
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