Dual regulation of the actin cytoskeleton by CARMIL-GAP.

Dual regulation of the actin cytoskeleton by CARMIL-GAP.
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DOI:
10.1242/jcs.258704
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发表时间:
2022-06-15
影响因子:
4
通讯作者:
Hammer JA
Hammer JA
中科院分区:
生物学2区
文献类型:
--
作者:
Jung G;Pan M;Alexander CJ;Jin T;Hammer JA

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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. Summary: Dictyostelium CARMIL-GAP supports phagocytosis and chemotaxis by regulating both capping protein and Rac1.
DOI: 10.1083/jcb.200810147
发表时间: 2009-08-24
期刊: The Journal of cell biology
影响因子: --
作者:
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通讯作者: Hammer JA 3rd
DOI: 10.1083/jcb.133.2.305
发表时间: 1996-04
期刊: The Journal of cell biology
影响因子: --
作者:
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通讯作者: Hammer JA 3rd
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影响因子: 11.1
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DOI: 10.4161/cib.27033
发表时间: 2013-11-01
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Davidson AJ;Insall RH
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