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Dual regulation of the actin cytoskeleton by CARMIL-GAP.
Jung, Goeh; Pan, Miao; Alexander, Christopher J; Jin, Tian; Hammer, John A.
Afiliación
  • Jung G; Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Pan M; Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD 20852, USA.
  • Alexander CJ; Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • Jin T; Chemotaxis Signal Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Disease, National Institutes of Health, Rockville, MD 20852, USA.
  • Hammer JA; Cell and Developmental Biology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA.
J Cell Sci ; 135(12)2022 06 15.
Article en En | MEDLINE | ID: mdl-35583107
Capping protein Arp2/3 myosin I linker (CARMIL) proteins are multi-domain scaffold proteins that regulate actin dynamics by regulating the activity of capping protein (CP). Here, we characterize CARMIL-GAP (GAP for GTPase-activating protein), a Dictyostelium CARMIL isoform that contains a ∼130 residue insert that, by homology, confers GTPase-activating properties for Rho-related GTPases. Consistent with this idea, this GAP domain binds Dictyostelium Rac1a and accelerates its rate of GTP hydrolysis. CARMIL-GAP concentrates with F-actin in phagocytic cups and at the leading edge of chemotaxing cells, and CARMIL-GAP-null cells exhibit pronounced defects in phagocytosis and chemotactic streaming. Importantly, these defects are fully rescued by expressing GFP-tagged CARMIL-GAP in CARMIL-GAP-null cells. Finally, rescue with versions of CARMIL-GAP that lack either GAP activity or the ability to regulate CP show that, although both activities contribute significantly to CARMIL-GAP function, the GAP activity plays the bigger role. Together, our results add to the growing evidence that CARMIL proteins influence actin dynamics by regulating signaling molecules as well as CP, and that the continuous cycling of the nucleotide state of Rho GTPases is often required to drive Rho-dependent biological processes.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Dictyostelium / Proteínas de Capping de la Actina Idioma: En Revista: J Cell Sci Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Dictyostelium / Proteínas de Capping de la Actina Idioma: En Revista: J Cell Sci Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos