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Am J Physiol Cell Physiol 288: C942-C949, 2005. First published December 8, 2004; doi:10.1152/ajpcell.00417.2004
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VASCULAR BIOLOGY

Expression of TRPC4 channel protein that interacts with NHERF-2 in rat descending vasa recta

Whaseon Lee-Kwon,1 James B. Wade,2 Zhong Zhang,1 Thomas L. Pallone,1,2 and Edward J. Weinman1,2,3

Departments of 1Medicine and 2Physiology, University of Maryland School of Medicine; and 3Department of Veterans Affairs Medical Center, Baltimore, Maryland

Submitted 24 August 2004 ; accepted in final form 6 December 2004

The PDZ domain adaptor protein Na+/H+ exchanger regulatory factor (NHERF)-2 is expressed in renal medullary descending vasa recta (DVR), although its function has not been defined. Transient receptor potential channels (TRPC) TRPC4 and TRPC5, nonselective cation channels that transport Ca2+, were recently demonstrated to complex with the NHERF proteins. We investigated whether TRPC4 and/or TRPC5 are associated with NHERF-2 in DVR. RT-PCR revealed mRNA for TRPC4 and NHERF-2, but not for TRPC5 or NHERF-1, in microdissected DVR. Immunohistochemical studies demonstrated expression of TRPC4 and NHERF-2 proteins in both the endothelial cells and pericytes. These proteins colocalized in some cells of the DVR. TRPC4 coimmunoprecipitated with NHERF-2 from renal medullary lysates, and NHERF-2 coimmunoprecipitated with TRPC4. TRPC5 was not detected in DVR with the use of immunohistochemistry or in NHERF-2 immunoprecipitates. We conclude that DVR pericytes and endothelia coexpress TRPC4 and NHERF-2 mRNA and protein and that these proteins colocalize and coimmunoprecipitate, indicating a possible physical association. These findings suggest that TRPC4 and NHERF-2 may play a role in interactions related to Ca2+ signaling.

PDZ proteins; calcium channels; medulla; pericytes; endothelium; microcirculation


Address for reprint requests and other correspondence: E. J. Weinman, Division of Nephrology, Department of Medicine, Univ. Maryland School of Medicine, N3W143, UMH, 22 S. Greene St., Baltimore, MD 21201 (E-mail: eweinman{at}medicine.umaryland.edu)




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