Journal article
GMF Severs Actin-Arp2/3 Complex Branch Junctions by a Cofilin-like Mechanism
Current biology, v 23(12), pp 1037-1045
17 Jun 2013
PMID: 23727094
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Branched actin filament networks driving cell motility, endocytosis, and intracellular transport are assembled in seconds by the Arp2/3 complex and must be equally rapidly debranched and turned over. One of the only factors known to promote debranching of actin networks is the yeast homolog of glia maturation factor (GMF), which is structurally related to the actin filament-severing protein cofilin. However, the identity of the molecular mechanism underlying debranching and whether this activity extends to mammalian GMF have remained open questions.
Results: Using scanning mutagenesis and total internal reflection fluorescence microscopy, we show that GMF depends on two separate surfaces for debranching. One is analogous to the G-actin and F-actin binding site on cofilin, but we show using fluorescence anisotropy and chemical crosslinking that it instead interacts with actin-related proteins in the Arp2/3 complex. The other is analogous to a second F-actin binding site on cofilin, which in GMF appears to contact the first actin subunit in the daughter filament. We further show that GMF binds to the Arp2/3 complex with low nanomolar affinity and promotes the open conformation. Finally, we show that this debranching activity and mechanism are conserved for mammalian GMF.
Conclusions: GMF debranches filaments by a mechanism related to cofilin-mediated severing, but in which GMF has evolved to target molecular junctions between actin-related proteins in the Arp2/3 complex and actin subunits in the daughter filament of the branch. This activity and mechanism are conserved in GMF homologs from evolutionarily distant species.
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Details
- Title
- GMF Severs Actin-Arp2/3 Complex Branch Junctions by a Cofilin-like Mechanism
- Creators
- Casey A. Ydenberg - Brandeis UniversityShae B. Padrick - The University of Texas Southwestern Medical CenterMeredith O. Sweeney - Brandeis UniversityMeghal Gandhi - Brandeis UniversityOlga Sokolova - Lomonosov Moscow State UniversityBruce L. Goode - Brandeis University
- Publication Details
- Current biology, v 23(12), pp 1037-1045
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- AstraZeneca 13-04-01570 / Russian Foundation for Basic Research; Russian Foundation for Basic Research (RFBR); Spanish Government Howard Hughes Medical Institute R01-GM56322; GM063691 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA I-1544 / Welch Foundation; The Welch Foundation 07.514.11.4125 / Ministry of Education and Science of the Russian Federation; Ministry of Education and Science, Russian Federation 11POST5830010 / American Heart Association
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000320682800016
- Scopus ID
- 2-s2.0-84879309319
- Other Identifier
- 991020836352504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Biology
- Cell Biology