The switch-associated protein 70 (SWAP-70) bundles actin filaments and contributes to the regulation of F-actin dynamics.
Coordinated assembly and disassembly of actin into filaments and higher order structures such as stress fibers and lamellipodia are fundamental for cell migration and adhesion. However, the precise spatiotemporal regulation of F-actin structures is not completely understood. SWAP-70, a phosphatidylinositol 3,4,5-trisphosphate-interacting, F-actin-binding protein, participates in actin rearrangements through yet unknown mechanisms. Here, we show that SWAP-70 is an F-actin-bundling protein that oligomerizes through a Gln/Glu-rich stretch within a coiled-coil region. SWAP-70 bundles filaments in parallel and anti-parallel fashion through its C-terminal F-actin binding domain and delays dilution-induced F-actin depolymerization. We further demonstrate that SWAP-70 co-localizes and directly interacts with cofilin, an F-actin severing and depolymerization factor, and contributes to the regulation of cofilin activity in vivo. In line with these activities, upon stem cell factor stimulation, murine bone marrow-derived mast cells lacking SWAP-70 display aberrant regulation of F-actin and actin free barbed ends dynamics. Moreover, proper stem cell factor-dependent cofilin activation via dephosphorylation and subcellular redistribution into a detergent-resistant cytoskeletal compartment also require SWAP-70. Together, these findings reveal an important role of SWAP-70 in the dynamic spatiotemporal regulation of F-actin networks.
From the Institute of Physiological Chemistry and.
Carlos Andrés
CA
Chacón-Martínez
Nadine
N
Kiessling
Moritz
M
Winterhoff
Jan
J
Faix
Thomas
T
Müller-Reichert
Rolf
R
Jessberger
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D015778:Minor Histocompatibility Antigens; D041681:NIH 3T3 Cells; D009687:Nuclear Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D058105:Polymerization / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects; D019089:Stem Cell Factor / Q000494:pharmacology; D034421:Sus scrofa
D051339:Actin Depolymerizing Factors; D000199:Actins; D004268:DNA-Binding Proteins; D020662:Guanine Nucleotide Exchange Factors; D008840:Microfilament Proteins; D015778:Minor Histocompatibility Antigens; D009687:Nuclear Proteins; D019089:Stem Cell Factor; C113365:Swap70 protein, mouse; C052523:actin filament bundling proteins
Actin; Cell Biology; Cofilin; Cytoskeleton; F-actin Bundling; Mast Cell; SWAP-70