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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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