Water transport across mammalian cell membranes.
Verkman, A. S., Alfred N. Van Hoek, Tonghui Ma, Antonio Frigeri, W. R.
Skach, Alok Mitra, B. K. Tamarappoo, and Javier Farinas.
Departments of Medicine and Physiology, Cardiovascular Research
Institute, University of California, San Francisco, CA, 94143-0521,
Department of Molecular and Cellular Engineering, University of
Pennsylvania, Philadelphia, PA, 19104, and Department of Cell
Biology, Scripps Research Institute, La Jolla, CA, 92037
APStracts 2:0263C, 1995.
This review summarizes recent progress in water transporting
mechanisms across cell membranes. Modern biophysical concepts of
water transport and new measurement strategies are evaluated. A
family of water transporting proteins (water channels, aquaporins)
has been identified, consisting of small hydrophobic proteins
expressed widely in epithelial and non-epithelial tissues. The
functional properties, genetics and cellular distributions of these
proteins are summarized. The majority of molecular-level information
about water transporting mechanisms comes from studies on CHIP28, a
28 kDa glycoprotein that forms tetramers in membranes; each monomer
contains 6 helical domains surrounding a central aqueous pathway, and
functions independently as a water-selective channel. Only mutations
in the vasopressin-sensitive water channel have been shown to cause
human disease - non-X-linked congenital, nephrogenic diabetes
insipidus; the physiological significance of other water channels
remains unproven. One mercurial-insensitive water channel has been
identified, which has the unique feature of multiple overlapping
transcriptional units. Systems for expression of water channel
proteins are described, including Xenopus oocytes, mammalian and
insect cells, and bacteria. Further work should be directed at
elucidation of the role of water channels in normal physiology and
disease, molecular analysis of regulatory mechanisms, and water
channel structure determination at atomic resolution.
Received 3 July 1995; accepted in final form 3 July 1995.
APS Manuscript Number C412-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.