EPLIN regulates actin dynamics by cross-linking and stabilizing filaments.
Epithelial protein lost in neoplasm (EPLIN) is a cytoskeleton-associated protein encoded by a gene that is down-regulated in transformed cells. EPLIN increases the number and size of actin stress fibers and inhibits membrane ruffling induced by Rac. EPLIN has at least two actin binding sites. Purified recombinant EPLIN inhibits actin filament depolymerization and cross-links filaments in bundles. EPLIN does not affect the kinetics of spontaneous actin polymerization or elongation at the barbed end, but inhibits branching nucleation of actin filaments by Arp2/3 complex. Side binding activity may stabilize filaments and account for the inhibition of nucleation mediated by Arp2/3 complex. We propose that EPLIN promotes the formation of stable actin filament structures such as stress fibers at the expense of more dynamic actin filament structures such as membrane ruffles. Reduced expression of EPLIN may contribute to the motility of invasive tumor cells.
Maul
Raymond S
RS
Department of Medicine, Immunology, and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Song
Yuhong
Y
Amann
Kurt J
KJ
Gerbin
Sachi C
SC
Pollard
Thomas D
TD
Chang
David D
DD
D008841:Actin Cytoskeleton / Q000378:metabolism*; D051377:Actin-Related Protein 2; D001665:Binding Sites / Q000502:physiology; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D015394:Molecular Structure; D009361:Neoplasm Invasiveness / Q000503:physiopathology*; D009369:Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D011108:Polymers; D011485:Protein Binding / Q000502:physiology; D011993:Recombinant Fusion Proteins; D013314:Stress, Mechanical; D014407:Tumor Cells, Cultured; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
C495926:ACTR2 protein, human; D051377:Actin-Related Protein 2; D003598:Cytoskeletal Proteins; C403263:LIMA1 protein, human; D011108:Polymers; D011993:Recombinant Fusion Proteins; D020830:rac1 GTP-Binding Protein