The C-terminal region of ahnak provides a link between cardiac L-type Ca2+ calcium channels and the actin-based cytoskeleton

Item Type:	Article
Title:	The C-terminal region of ahnak provides a link between cardiac L-type Ca2+ calcium channels and the actin-based cytoskeleton
Creators Name:	Hohaus, A. and Person, V. and Behlke, J. and Schaper, J. and Morano, I. and Haase, H.
Abstract:	Ahnak is a ubiquitously expressed giant protein of 5643 amino acids implicated in cell differentiation and signal transduction. In a recent study, we demonstrated the association of ahnak with the regulatory {beta}2 subunit of the cardiac L-type Ca2+ channel. Here we identify the most carboxyl-terminal ahnak region (aa 5262-5643) to interact with recombinant {beta}2a as well as with {beta}2 and {beta}1a isoforms of native muscle Ca2+ channels using a panel of GST fusion proteins. Equilibrium sedimentation analysis revealed Kd values of 55 ± 11 nM and 328 ± 24 nM for carboxyl-terminal (aa 195-606) and amino-terminal (aa 1-200) truncates of the {beta}2a subunit, respectively. The same carboxyl terminal ahnak region (aa 5262-5643) bound to G-actin and cosedimented with F-actin. Confocal microscopy of human left ventricular tissue localized the carboxyl terminal ahnak portion to the sarcolemma including the T-tubular system and the intercalated disks of cardiomyocytes. These results suggest that ahnak provides a structural basis for the subsarcolemmal cytoarchitecture and confers the regulatory role of the actin-based cytoskeleton to the L-type Ca2+ channel.
Keywords:	{Beta}3 Subunit, Cardiomyocytes, L-Type Calcium Channel, Protein-Protein Interaction, Animals, Swine
Source:	FASEB Journal
ISSN:	0892-6638
Publisher:	Federation of American Societies for Experimental Biology
Volume:	16
Number:	10
Page Range:	1205-1216
Date:	August 2002
Official Publication:	https://doi.org/10.1096/fj.01-0855com
PubMed:	View item in PubMed

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