Am. J. Respir. Cell Mol. Biol., Volume 19, Number 1, July, 1998 143-149

Evidence against a Role of Mouse, Rat, and Two Cloned Human T1 Isoforms as a Water Channel or a Regulator of Aquaporin-type Water Channels

Tonghui Ma, Baoxue Yang, Michael A. Matthay, and A. S. Verkman

Departments of Medicine and Physiology, Cardiovascular Research Institute, University of California, San Francisco, California

T1 is a protein of unknown function that is expressed at the plasma membrane in epithelia involved in fluid transport, including type I alveolar epithelial cells, choroid plexus, and ciliary epithelium. The purpose of this study was to test the hypothesis that T1 functions as a water channel or a regulator of aquaporin-type water channels that are coexpressed with T1. Two complementary DNAs (cDNAs) (hT1-1 and hT1-2) encoding human isoforms of T1 were cloned by homology to the rat T1 coding sequence. The cDNAs encoded 164 (hT1-1) and 162 (hT1-2) amino acid proteins with high homology to rat T1 in a putative membrane-spanning domain. hT1-1 transcripts of 2.6 and 1.4 kb were detected in human lung, heart, and skeletal muscle, and a single hT1-2 transcript of 1.2 kb was detected in human lung. Rat and mouse T1 were isolated by reverse transcription-polymerase chain reaction and confirmed by DNA sequence analysis. Expression of mouse, rat, and human T1 isoforms in Xenopus oocytes did not increase osmotic water permeability (P_f) above that in water-injected oocytes, nor was there an effect of protein kinase A or C activation; P_f was increased > 10-fold in positive control oocytes expressing aquaporin (AQP)1 or AQP5. Coexpression of AQP1 or AQP5 with excess T1 gave P_f not different from that in oocytes expressing AQP1 or AQP5 alone. Oocyte plasma membrane localization of epitope-tagged T1 protein was confirmed and quantified by immunoprecipitation of microdissected plasma membranes. Quantitative densitometry indicated that the single-channel water permeability of T1 is under 2 × 10¹⁶ cm³/s, suggesting that T1 is not involved in the high transalveolar water permeability in intact lung. The cloning of hT1 isoforms may permit the development of an assay of type I cell antigen in airspace fluid as a marker of human lung injury.

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