Spatial association of the Cav1.2 calcium channel with α5β1-integrin

Simple item page
dc.contributor.authorChao, Juntzu
dc.contributor.authorGui, Peichun
dc.contributor.authorZamponi, Gerald W.
dc.contributor.authorDavis, George E.
dc.contributor.authorDavis, Michael J.
dc.date.accessioned2018-05-29T20:34:52Z
dc.date.available2018-05-29T20:34:52Z
dc.date.issued2010-12-22
dc.description.abstractEngagement of α(5)β(1)-integrin by fibronectin (FN) acutely enhances Cav1.2 channel (Ca(L)) current in rat arteriolar smooth muscle and human embryonic kidney cells (HEK293-T) expressing Ca(L). Using coimmunoprecipitation strategies, we show that coassociation of Ca(L) with α(5)- or β(1)-integrin in HEK293-T cells is specific and depends on cell adhesion to FN. In rat arteriolar smooth muscle, coassociations between Ca(L) and α(5)β(1)-integrin and between Ca(L) and phosphorylated c-Src are also revealed and enhanced by FN treatment. Using site-directed mutagenesis of Ca(L) heterologously expressed in HEK293-T cells, we identified two regions of Ca(L) required for these interactions: 1) COOH-terminal residues Ser(1901) and Tyr(2122), known to be phosphorylated by protein kinase A (PKA) and c-Src, respectively; and 2) two proline-rich domains (PRDs) near the middle of the COOH terminus. Immunofluorescence confocal imaging revealed a moderate degree of wild-type Ca(L) colocalization with β(1)-integrin on the plasma membrane. Collectively, our results strongly suggest that 1) upon ligation by FN, Ca(L) associates with α(5)β(1)-integrin in a macromolecular complex including PKA, c-Src, and potentially other protein kinases; 2) phosphorylation of Ca(L) at Y(2122) and/or S(1901) is required for association of Ca(L) with α(5)β(1)-integrin; and 3) c-Src, via binding to PRDs that reside in the II-III linker region and/or the COOH terminus of Ca(L), mediates current potentiation following α(5)β(1)-integrin engagement. These findings provide new evidence for how interactions between α(5)β(1)-integrin and FN can modulate Ca(L) entry and consequently alter the physiological function of multiple types of excitable cells.en_US
dc.identifier.citationChao, J.-T., Gui, P., Zamponi, G. W., Davis, G. E., & Davis, M. J. (2011). Spatial association of the Cav1.2 calcium channel with α5β1-integrin. American Journal of Physiology. Cell Physiology, 300(3), C477-89. https://doi.org/10.1152/ajpcell.00171.2010en_US
dc.identifier.doihttp://dx.doi.org/10.1152/ajpcell.00171.2010en_US
dc.identifier.urihttp://hdl.handle.net/1880/106709
dc.language.isoenen_US
dc.publisherAmerican Physiological Societyen_US
dc.publisher.departmentPhysiology & Pharmacologyen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleSpatial association of the Cav1.2 calcium channel with α5β1-integrinen_US
dc.typejournal articleen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Chao et al 2011 AJP.pdf
Size:
1.67 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
1.92 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Cumming School of Medicine Research & Publications