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Title: Alternative splicing of ClC-6 (a member of the CIC chloride-channel family) transcripts generates three truncated isoforms one of which, ClC-6c, is kidney-specific
Authors: Eggermont, Jan ×
Buyse, Gunnar
Voets, Thomas
Tytgat, Jan
De Smedt, Humbert
Droogmans, Guillaume
Nilius, Bernd #
Issue Date: Jul-1997
Series Title: The Biochemical journal. vol:325 ( Pt 1) pages:269-76
Abstract: ClC-6 is a protein that structurally belongs to the family of ClC-type chloride channels. We now report the identification of three additional ClC-6 isoforms that are truncated because of alternative splicing. We have isolated, from human K562 cells, four types of ClC-6 cDNAs that encode four distinct ClC-6 protein isoforms. ClC-6a (869 amino acids) corresponds to the previously published ClC-6 protein [Brandt and Jentsch (1995) FEBS Lett. 377, 15-20] and it has a canonical ClC structure. However, ClC-6b (320 amino acids), ClC-6c (353 amino acids) and ClC-6d (308 amino acids) are truncated at their C-termini. Hydropathy-plot analysis indicates that the shortened isoforms contain maximally four (ClC-6b and -6d) or seven (ClC-6c) transmembrane domains. Sequence analysis of a human genomic ClC-6 fragment indicates that the cDNA variability arises from alternative splicing at two different positions: the first alternative site consists of an intron flanked by two alternative donor sites and two alternative acceptor sites, the second being due to an exon that is optionally included or excluded. Reverse-transcription-PCR analysis of ClC-6 expression in human cell lines and tissues shows that the majority (83%) of ClC-6 mRNAs consists of ClC-6a or ClC-6c messengers. Furthermore, in a mouse tissue panel, the ClC-6a mRNA has a relatively broad tissue expression pattern, since it could be detected in brain, kidney, testis, skeletal muscle, thymus and pancreas. In contrast, expression of ClC-6c is more restricted, since it was only detected in kidney.
URI: 
ISSN: 0264-6021
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Physiology Section (-)
Toxicology and Pharmacology
Laboratory of Molecular and Cellular Signaling
Laboratory of Ion Channel Research
Brain & Metabolism Section (-)
Department of Cellular and Molecular Medicine - miscellaneous
Laboratory of Cellular Transport Systems
× corresponding author
# (joint) last author

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