TY - JOUR
T1 - The cell polarity protein minsc regulates neutrophil chemotaxis via a noncanonical G protein signaling pathway
AU - Kamakura, Sachiko
AU - Nomura, Masatoshi
AU - Hayase, Junya
AU - Iwakiri, Yuko
AU - Nishikimi, Akihiko
AU - Takayanagi, Ryoichi
AU - Fukui, Yoshinori
AU - Sumimoto, Hideki
N1 - Funding Information:
We thank M. Nakao for providing the plasmid for ubiquitin, N. Kubo, Y. Kage, and N. Morinaga for technical assistance, K. Terasawa and A.T. Sasaki for technical advice and helpful discussion, and M. Nishinou for secretarial assistance. We are also grateful for technical support from the Research Support Center, Kyushu University Graduate School of Medical Sciences, and from the Laboratory for Technical Support, Medical Institute of Bioregulation, Kyushu University. This work was supported in part by the Ministry of Education, Culture, Sports, Science and Technology (MEXT) KAKENHI grant number 20117002, Japan Society for the Promotion of Science (JSPS) KAKENHI grant number 24590385, and the Astellas Foundation for Research on Metabolic Disorders.
PY - 2013/8/12
Y1 - 2013/8/12
N2 - 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 Gproteins, directional movement is regulated by mInsc, a mammalian protein distantly related to the. Drosophila polarity-organizer Inscuteable. The GDP-bound, Gβγ-free Gαi 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 Gαi-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 Gβγ-free Gαi-GDP, a product from Gαi-GTP released after receptor activation, plays a central role.
AB - 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 Gproteins, directional movement is regulated by mInsc, a mammalian protein distantly related to the. Drosophila polarity-organizer Inscuteable. The GDP-bound, Gβγ-free Gαi 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 Gαi-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 Gβγ-free Gαi-GDP, a product from Gαi-GTP released after receptor activation, plays a central role.
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U2 - 10.1016/j.devcel.2013.06.008
DO - 10.1016/j.devcel.2013.06.008
M3 - Article
C2 - 23891662
AN - SCOPUS:84881546973
SN - 1534-5807
VL - 26
SP - 292
EP - 302
JO - Developmental Cell
JF - Developmental Cell
IS - 3
ER -