Activation of Na+-H+ exchange is necessary for RhoA-induced stress fiber formation.
The ubiquitously expressed Na+-H+ exchanger isoform, NHE1, functions in regulating intracellular pH and cell volume. We recently determined that the GTPase Galpha13 stimulates NHE1 activity through a RhoA-dependent mechanism (Hooley, R., Yu, C.-Y., Symons, M., and Barber, D. L. (1996) J. Biol. Chem. 271, 6152-6158). RhoA belongs to the Ras superfamily of GTPases and is a key regulator of actin stress fiber formation. We therefore investigated the relationship between RhoA, NHE1 activity, and the regulation of stress fiber assembly. Using two independent approaches, pharmacological inhibition of NHE1 and NHE1-deficient cells, we determined that the induction of stress fibers by lysophosphatidic acid and RhoA is dependent on increased NHE1 activity. These results indicate that stimulation of NHE1 acts downstream of RhoA in a pathway that controls stress fiber formation.
Vexler
Z S
ZS
Department of Stomatology, University of California, San Francisco, California 94143, USA.
Symons
M
M
Barber
D L
DL
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006146:Guanidines / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D008246:Lysophospholipids / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D015398:Signal Transduction; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D020742:rhoA GTP-Binding Protein
D000199:Actins; D006146:Guanidines; D008246:Lysophospholipids; D017923:Sodium-Hydrogen Exchangers; D013450:Sulfones; C069139:growth factor-activatable Na-H exchanger NHE-1; C074107:3-methylsulfonyl-4-piperidinobenzoyl guanidine; D019204:GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein