A Rho-dependent signaling pathway operating through myosin localizes beta-actin mRNA in fibroblasts.
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 Rho 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 II-B-dependent step and postulate that polarized actin bundles direct the mRNA to the leading edge of the cell.
Latham
V M
VM
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Yu
E H
EH
Tullio
A N
AN
Adelstein
R S
RS
Singer
R H
RH
D000199:Actins / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D016764:Cell Polarity; D002478:Cells, Cultured; D002642:Chick Embryo; D005347:Fibroblasts / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009218:Myosins / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000502:physiology*; D054460:rho-Associated Kinases
D000199:Actins; D047908:Intracellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D009218:Myosins; D020741:rho GTP-Binding Proteins