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dc.contributor.authorBeaulieu, Valerie  Concept link
dc.contributor.authorDa Silva, Nicolas  Concept link
dc.contributor.authorPastor-Soler, Nuria  Concept link
dc.contributor.authorBrown, Christopher R.  Concept link
dc.contributor.authorSmith, Peter J. S.  Concept link
dc.contributor.authorBrown, Dennis  Concept link
dc.contributor.authorBreton, Sylvie  Concept link
dc.date.accessioned2009-04-24T18:54:27Z
dc.date.available2009-04-24T18:54:27Z
dc.date.issued2004-12-09
dc.identifier.citationJournal of Biological Chemistry 280 (2005): 8452-8463en
dc.identifier.urihttps://hdl.handle.net/1912/2809
dc.descriptionAuthor Posting. © American Society for Biochemistry and Molecular Biology, 2005. This article is posted here by permission of American Society for Biochemistry and Molecular Biology for personal use, not for redistribution. The definitive version was published in Journal of Biological Chemistry 280 (2005): 8452-8463, doi:10.1074/jbc.M412750200.en
dc.description.abstractThe role of the actin cytoskeleton in regulating membrane protein trafficking is complex and depends on the cell type and protein being examined. Using the epididymis as a model system in which luminal acidification is crucial for sperm maturation and storage, we now report that modulation of the actin cytoskeleton by the calcium-activated actin-capping and -severing protein gelsolin plays a key role in regulating vacuolar H+-ATPase (V-ATPase) recycling. Epididymal clear cells contain abundant V-ATPase in their apical pole, and an increase in their cell-surface V-ATPase expression correlates with an increase in luminal proton secretion. We have shown that apical membrane accumulation of V-ATPase is triggered by an elevation in cAMP following activation of bicarbonate-regulated soluble adenylyl cyclase in response to alkaline luminal pH (Pastor-Soler, N., Beaulieu, V., Litvin, T. N., Da Silva, N., Chen, Y., Brown, D., Buck, J., Levin, L. R., and Breton, S. (2003) J. Biol. Chem. 278, 49523-49529). Here, we show that clear cells express high levels of gelsolin, indicating a potential role in the functional activity of these cells. When jasplakinolide was used to overcome the severing action of gelsolin by polymerizing actin, complete inhibition of the alkaline pH- and cAMP-induced apical membrane accumulation of V-ATPase was observed. Conversely, when gelsolin-mediated actin filament elongation was inhibited using a 10-residue peptide (PBP10) derived from the phosphatidylinositol 4,5-bisphosphate-binding region (phosphoinositide-binding domain 2) of gelsolin, significant V-ATPase apical membrane mobilization was induced, even at acidic luminal pH. In contrast, the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) and the phospholipase C inhibitor U-73122 inhibited the alkaline pH-induced V-ATPase apical accumulation. Thus, maintenance of the actin cytoskeleton in a depolymerized state by gelsolin facilitates calcium-dependent apical accumulation of V-ATPase in response to luminal pH alkalinization. Gelsolin is present in other cell types that express the V-ATPase in their plasma membrane and recycling vesicles, including kidney intercalated cells and osteoclasts. Therefore, modulation of the actin cortex by this severing and capping protein may represent a common mechanism by which these cells regulate their rate of proton secretion.en
dc.description.sponsorshipThis work was supported by National Institutes of Health Grants HD40793 (to S. B.), DK38452 (to D. B. and S. B.), DK42956 (to D. B.), P41-RR001395 (to P. J. S. S.), and KO8-HD45524 (to N.P.-S.) and National Research Service Award HD08684 (to N. P.-S.). The work performed in the Microscopy Core Facility of the Massachusetts General Hospital Program in Membrane Biology was supported by Center for the Study of Inflammatory Bowel Disease Grant DK43351 and Boston Area Diabetes and Endocrinology Research Center Award DK57521.en
dc.format.mimetypeapplication/pdf
dc.language.isoen_USen
dc.publisherAmerican Society for Biochemistry and Molecular Biologyen
dc.relation.urihttps://doi.org/10.1074/jbc.M412750200
dc.titleModulation of the actin cytoskeleton via gelsolin regulates aacuolar H+-ATPase recyclingen
dc.typeArticleen
dc.identifier.doi10.1074/jbc.M412750200


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