期刊
EMBO JOURNAL
卷 31, 期 4, 页码 1028-1040出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/emboj.2011.464
关键词
actin filaments; cell migration; oskar mRNA; RhoA; Smurf1
资金
- Child Health Research Center [HD052890]
- NIH [DK57683, DK062472, EY14597]
Tropomyosins are widespread actin-binding proteins that influence numerous cellular functions including actin dynamics, cell migration, tumour suppression, and Drosophila oocyte development. Synaptopodin is another actin-binding protein with a more restricted expression pattern in highly dynamic cell compartments such as kidney podocyte foot processes, where it promotes RhoA signalling by blocking the Smurf1-mediated ubiquitination of RhoA. Here, we show that synaptopodin has a shorter half-life but shares functional properties with the highly stable tropomyosin. Transgenic expression of synaptopodin restores oskar mRNA localization in Drosophila oocytes mutant for TmII, thereby rescuing germline differentiation and fertility. Synaptopodin restores stress fibres in tropomyosin-deficient human MDA-MB 231 breast cancer cells and TPM alpha-depleted fibroblasts. Gene silencing of TPM alpha but not TPM beta causes loss of stress fibres by promoting Smurf1-mediated ubiquitination and proteasomal degradation of RhoA. Functionally, overexpression of synaptopodin or RhoA(K6,7R) significantly reduces MDA-MB 231 cell migration. Our findings elucidate RhoA stabilization by structurally unrelated actin-binding proteins as a conserved mechanism for regulation of stress fibre dynamics and cell motility in a cell type-specific fashion. The EMBO Journal (2012) 31, 1028-1040. doi: 10.1038/emboj.2011.464; Published online 13 December 2011
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