RRC ID 55963
著者 Fujiwara S, Matsui TS, Ohashi K, Deguchi S, Mizuno K.
タイトル Solo, a RhoA-targeting guanine nucleotide exchange factor, is critical for hemidesmosome formation and acinar development in epithelial cells.
ジャーナル PLoS One
Abstract Cell-substrate adhesions are essential for various physiological processes, including embryonic development and maintenance of organ functions. Hemidesmosomes (HDs) are multiprotein complexes that attach epithelial cells to the basement membrane. Formation and remodeling of HDs are dependent on the surrounding mechanical environment; however, the upstream signaling mechanisms are not well understood. We recently reported that Solo (also known as ARHGEF40), a guanine nucleotide exchange factor targeting RhoA, binds to keratin8/18 (K8/K18) intermediate filaments, and that their interaction is important for force-induced actin and keratin cytoskeletal reorganization. In this study, we show that Solo co-precipitates with an HD protein, β4-integrin. Co-precipitation assays revealed that the central region (amino acids 330-1057) of Solo binds to the C-terminal region (1451-1752) of β4-integrin. Knockdown of Solo significantly suppressed HD formation in MCF10A mammary epithelial cells. Similarly, knockdown of K18 or treatment with Y-27632, a specific inhibitor of Rho-associated kinase (ROCK), suppressed HD formation. As Solo knockdown or Y-27632 treatment is known to disorganize K8/K18 filaments, these results suggest that Solo is involved in HD formation by regulating K8/K18 filament organization via the RhoA-ROCK signaling pathway. We also showed that knockdown of Solo impairs acinar formation in MCF10A cells cultured in 3D Matrigel. In addition, Solo accumulated at the site of traction force generation in 2D-cultured MCF10A cells. Taken together, these results suggest that Solo plays a crucial role in HD formation and acinar development in epithelial cells by regulating mechanical force-induced RhoA activation and keratin filament organization.
巻・号 13(4)
ページ e0195124
公開日 2018-4-19
DOI 10.1371/journal.pone.0195124
PII PONE-D-17-44324
PMID 29672603
PMC PMC5909619
MeSH Acinar Cells / metabolism* Animals Cell Line Epithelial Cells / metabolism* Gene Expression Gene Knockdown Techniques Guanine Nucleotide Exchange Factors / chemistry Guanine Nucleotide Exchange Factors / genetics Guanine Nucleotide Exchange Factors / metabolism* Hemidesmosomes / metabolism* Humans Integrin beta4 / chemistry Integrin beta4 / metabolism Keratin-18 / genetics Keratin-18 / metabolism Protein Binding Protein Interaction Domains and Motifs Signal Transduction
IF 2.776
引用数 5
リソース情報
ヒト・動物細胞 COS-7(RCB0539)