Journal article
Septin 9 exhibits polymorphic binding to F-actin and inhibits myosin and cofilin activity
Journal of molecular biology, v 427(20), pp 3273-3284
09 Oct 2015
PMID: 26297986
Abstract
Septins are a highly conserved family of proteins in eukaryotes that is recognized as a novel component of the cytoskeleton. Septin 9 (SEPT9) interacts directly with actin filaments and functions as an actin stress fiber cross-linking protein that promotes the maturation of nascent focal adhesions and cell migration. However, the molecular details of how SEPT9 interacts with F-actin remain unknown. Here, we use electron microscopy and image analysis to show that SEPT9 binds to F-actin in a highly polymorphic fashion. We demonstrate that the basic domain (B-domain) of the N-terminal tail of SEPT9 is responsible for actin cross-linking, while the GTP-binding domain (G-domain) does not bundle F-actin. We show that the B-domain of SEPT9 binds to three sites on F-actin, and the two of these sites overlap with the binding regions of myosin and cofilin. SEPT9 inhibits actin-dependent ATPase activity of myosin and competes with the weakly-bound state of myosin for binding to F-actin. At the same time, SEPT9 significantly reduces the extent of F-actin depolymerization by cofilin. Taken together, these data suggest that SEPT9 protects actin filaments from depolymerization by cofilin and myosin, and indicate a mechanism by which SEPT9 could maintain the integrity of growing and contracting actin filaments.
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Details
- Title
- Septin 9 exhibits polymorphic binding to F-actin and inhibits myosin and cofilin activity
- Creators
- Clayton Smith - Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, USALee Dolat - Department of Biology, Drexel University, Philadelphia, PA 19104, USADimitrios Angelis - Department of Biology, Drexel University, Philadelphia, PA 19104, USAEva Forgacs - Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, USAElias T Spiliotis - Department of Biology, Drexel University, Philadelphia, PA 19104, USAVitold E Galkin - Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23507, USA
- Publication Details
- Journal of molecular biology, v 427(20), pp 3273-3284
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biology; Pediatrics
- Web of Science ID
- WOS:000362611300007
- Scopus ID
- 2-s2.0-84943664350
- Other Identifier
- 991014877669304721
InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology