spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online July 17, 2009
Journal of Experimental Biology 212, 2365-2377 (2009)
Published by The Company of Biologists 2009
doi: 10.1242/jeb.030015
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Marshall, W. S.
Right arrow Articles by Katoh, F.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Marshall, W. S.
Right arrow Articles by Katoh, F.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

CFTR Cl– channel functional regulation by phosphorylation of focal adhesion kinase at tyrosine 407 in osmosensitive ion transporting mitochondria rich cells of euryhaline killifish

William S. Marshall*, Kaitlyn D. Watters, Leah R. Hovdestad, Regina R. F. Cozzi and Fumi Katoh

Department of Biology, St Francis Xavier University, PO Box 5000 Antigonish, Nova Scotia, Canada B2G 2W5

* Author for correspondence (e-mail: bmarshal{at}stfx.ca)

Accepted 6 May 2009

Cystic fibrosis transmembrane conductance regulator (CFTR) anion channels are the regulated exit pathway in Cl– secretion by teleost mitochondria rich salt secreting (MR) cells of the gill and opercular epithelia of euryhaline teleosts. By confocal light immunocytochemistry, immunogold transmission electron microscopy (TEM), and co-immunoprecipitation, using regular and phospho-antibodies directed against conserved sites, we found that killifish CFTR (kfCFTR) and the tyrosine kinase focal adhesion kinase (FAK) phosphorylated at Y407 (FAK pY407) are colocalized in the apical membrane and in subjacent membrane vesicles of MR cells. We showed previously that basolateral FAK pY407, unlike other FAK phosphorylation sites, is osmosensitive and dephosphorylates during hypotonic shock of epithelial cells (Marshall et al., 2008). In the present study, we found that hypotonic shock and the {alpha}2-adrenergic agonist clonidine (neither of which affects cAMP levels) rapidly and reversibly inhibit Cl– secretion by isolated opercular membranes, simultaneous with dephosphorylation of FAK pY407, located in the apical membrane. FAK pY407 is rephosphorylated and Cl– secretion rapidly restored by hypertonic shock as well as by forskolin and isoproterenol, which operate via cAMP and protein kinase A. We conclude that hormone mediated, cAMP dependent and osmotically mediated, cAMP independent pathways converge on a mechanism to activate CFTR and Cl– secretion, possibly through tyrosine phosphorylation of CFTR by FAK.

Key words: cystic fibrosis transmembrane conductance regulator (CFTR), tyrosine phosphorylation, epithelial transport, teleost osmoregulation, metabolon, ion channel regulation, hypotonic, focal adhesion kinase (FAK)


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




© The Company of Biologists Ltd 2009