Am J Physiol Cell Physiol AJP: Regulatory, Integrative and Comparative Physiology
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Am J Physiol Cell Physiol 280: C373-C381, 2001;
0363-6143/01 $5.00
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Vol. 280, Issue 2, C373-C381, February 2001

Tissue distribution and subcellular localization of the ClC-5 chloride channel in rat intestinal cells

Alain Vandewalle1, Françoise Cluzeaud1, Kou-Cheng Peng1, Marcelle Bens1, Anke Lüchow2, Willy Günther2, and Thomas J. Jentsch2

1 Institut National de la Santé et de la Recherche Médicale, Unité 478, Institut Fédératif de Recherche 02, Faculté de Médecine Xavier Bichat, BP 416, 75870 Paris Cedex 18, France; and 2 Zentrum für Molekulare Neurobiologie Hamburg, Universität Hamburg, Martinistrasse 85, D-20246 Hamburg, Germany

ClC-5 is the Cl- channel that is mutated in Dent's disease, an X-chromosome-linked disease characterized by low molecular weight proteinuria, hypercalciuria, and kidney stones. It is predominantly expressed in endocytically active renal proximal cells. We investigated whether this Cl- channel could also be expressed in intestinal tissues that have endocytotic machinery. ClC-5 mRNA was detected in the rat duodenum, jejunum, ileum, and colon. Western blot analyses revealed the presence of the 83-kDa ClC-5 protein in these tissues. Indirect immunofluorescence studies showed that ClC-5 was mainly concentrated in the cytoplasm above the nuclei of enterocytes and colon cells. ClC-5 partially colocalized with the transcytosed polymeric immunoglobulin receptor but was not detectable together with the brush-border-anchored sucrase isomaltase. A subfractionation of vesicles obtained by differential centrifugation showed that ClC-5 is associated with the vacuolar 70-kDa H+-ATPase and the small GTPases rab4 and rab5a, two markers of early endosomes. Thus these results indicate that ClC-5 is present in the small intestine and colon of rats and suggest that it plays a role in the endocytotic pathways of intestinal cells.

intestine; endocytosis; H+-ATPase; rab


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