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Nonmuscle myosin IIA (myosin heavy polypeptide 9): a novel class of signal transducer mediating the activation of G alpha h/phospholipase C-delta 1 pathway.

Authors: Lin, YF  Yeh, TS  Chen, SF  Tsai, YH  Chou, CM  Yang, YY  Huang, HM 
Citation: Lin YF, etal., Endocrinology. 2010 Mar;151(3):876-85. Epub 2010 Jan 12.
Pubmed: (View Article at PubMed) PMID:20068007
DOI: Full-text: DOI:10.1210/en.2009-0722

The dimeric Gh protein is comprised of alpha (tissue transglutaminase) and beta (Calreticulin) subunits and known to be associated with FSH-, oxytocin-, or epinephrine-receptors/functions in their respective target cells. After establishing the FSH-induced activation of G alpha h/phospholipase C (PLC)-delta 1 pathway in rat Sertoli cells (SCs), we have attempted to identify a possible G alpha h-coupled novel FSH receptor (FSH-R). Remarkably, a protein with approximately 240-kDa molecular mass was coimmunoprecipitated with G alpha h in the fractionated membrane proteins of rat SCs. The protein was identified as myosin heavy polypeptide 9 (MyH9) by mass spectrometric analysis and immunoblotting. In addition, immunoprecipitation analysis reveals that MyH9 is constitutively associated with classical Gs-coupled FSH-R and inactive GDP-bound G alpha h at resting state of rat SCs, but did not interact with FSH directly as judged by Far-Western analysis. Upon the stimulation of higher levels of extracellular FSH (>1000 IU/liter), classical FSH-R induces the phosphorylation of MyH9, the dissociation of active GTP-bound G alpha h from FSH-R:MyH9 complexes, and the elicitation of G alpha h/PLC-delta 1 pathway-dependent Ca(2+)-influx in rat SCs. Furthermore, the specific inhibition of MyH9 ATPase activity with Blebbistatin dose-dependently suppressed FSH-induced G alpha h/PLC-delta 1 signaling and Ca(2+)-influx, but not intracellular cAMP accumulation in rat SCs, implying that MyH9 mediates FSH-induced activation of G alpha h/PLC-delta 1/IP(3)/Ca(2+)-influx pathway in rat SCs. This is the first to demonstrate that the filament protein MyH9 constitutively forms a ternary complex with FSH-R and inactive GDP-bound G alpha h. At higher FSH levels, this ternary complex executes an alternative signaling of classical Gs-coupled FSH-R through activating a Gs/cAMP-independent, G alpha h/PLC-delta 1 pathway in rat SCs.

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CRRD Object Information
CRRD ID: 6902910
Created: 2012-09-21
Species: All species
Last Modified: 2012-09-21
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.