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Septins promote stress fiber-mediated maturation of focal adhesions and renal epithelial motility
Journal article   Open access   Peer reviewed

Septins promote stress fiber-mediated maturation of focal adhesions and renal epithelial motility

Lee Dolat, John L Hunyara, Jonathan R Bowen, Eva Pauline Karasmanis, Maha Elgawly, Vitold E Galkin and Elias T Spiliotis
The Journal of cell biology, v 207(2)
27 Oct 2014
PMID: 25349260
url
https://doi.org/10.1083/jcb.201405050View
Published, Version of Record (VoR) Open

Abstract

Up-Regulation Cells, Cultured Kidney - cytology Septins - analysis Kidney - metabolism Stress Fibers - metabolism Animals Focal Adhesions - metabolism Dogs Epithelial-Mesenchymal Transition Focal Adhesions - ultrastructure Septins - physiology Septins - metabolism Cell Movement
Organogenesis and tumor metastasis involve the transformation of epithelia to highly motile mesenchymal-like cells. Septins are filamentous G proteins, which are overexpressed in metastatic carcinomas, but their functions in epithelial motility are unknown. Here, we show that a novel network of septin filaments underlies the organization of the transverse arc and radial (dorsal) stress fibers at the leading lamella of migrating renal epithelia. Surprisingly, septin depletion resulted in smaller and more transient and peripheral focal adhesions. This phenotype was accompanied by a highly disorganized lamellar actin network and rescued by the actin bundling protein α-actinin-1. We show that preassembled actin filaments are cross-linked directly by Septin 9 (SEPT9), whose expression is increased after induction of renal epithelial motility with the hepatocyte growth factor. Significantly, SEPT9 overexpression enhanced renal cell migration in 2D and 3D matrices, whereas SEPT9 knockdown decreased migration. These results suggest that septins promote epithelial motility by reinforcing the cross-linking of lamellar stress fibers and the stability of nascent focal adhesions.

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Collaboration types
Domestic collaboration
Web of Science research areas
Cell Biology
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