A Rho-dependent signaling pathway operating through myosin localizes β-actin mRNA in fibroblasts

被引:75
作者
Latham, VM
Yu, EHS
Tullio, AN
Adelstein, RS
Singer, RH
机构
[1] Yeshiva Univ Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA
[2] NHLBI, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1016/S0960-9822(01)00291-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: The sorting of mRNA is a determinant of cell asymmetry. The cellular signals that direct specific RNA sequences to a particular cellular compartment are unknown. In fibroblasts, beta -actin mRNA has been shown to be localized toward the leading edge, where it plays a role in cell motility and asymmetry. Results: We demonstrate that a signaling pathway initiated by extracellular receptors, acting through Rho GTPase and Rho-kinase regulates this spatial aspect of gene expression in fibroblasts by localizing beta -actin mRNA via actomyosin interactions Consistent with the role of Rha as an activator of myosin, we found that inhibition of myosin ATPase, myosin light chain kinase (MLCK), and the knockout of myosin II-B in mouse embryonic fibroblasts all inhibited beta -actin mRNA from localizing in response to growth factors. Conclusions: We therefore conclude that the sorting of beta -actin mRNA in fibroblasts requires a Rho mediated pathway operating through a myosin Il-B-dependent step and postulate that polarized actin bundles direct the mRNA to the leading edge of the cell.
引用
收藏
页码:1010 / 1016
页数:7
相关论文
共 34 条
[31]   Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts [J].
Totsukawa, G ;
Yamakita, Y ;
Yamashiro, S ;
Hartshorne, DJ ;
Sasaki, Y ;
Matsumura, F .
JOURNAL OF CELL BIOLOGY, 2000, 150 (04) :797-806
[32]   Nonmuscle myosin II-B is required for normal development of the mouse heart [J].
Tullio, AN ;
Accili, D ;
Ferrans, VJ ;
Yu, ZX ;
Takeda, K ;
Grinberg, A ;
Westphal, H ;
Preston, YA ;
Adelstein, RS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (23) :12407-12412
[33]   Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension [J].
Uehata, M ;
Ishizaki, T ;
Satoh, H ;
Ono, T ;
Kawahara, T ;
Morishita, T ;
Tamakawa, H ;
Yamagami, K ;
Inui, J ;
Maekawa, M ;
Narumiya, S .
NATURE, 1997, 389 (6654) :990-994
[34]   EFFECT OF PROTEIN-KINASE INHIBITOR H-7 ON THE CONTRACTILITY, INTEGRITY, AND MEMBRANE ANCHORAGE OF THE MICROFILAMENT SYSTEM [J].
VOLBERG, T ;
GEIGER, B ;
CITI, S ;
BERSHADSKY, AD .
CELL MOTILITY AND THE CYTOSKELETON, 1994, 29 (04) :321-338