Journal
BIOPHYSICAL JOURNAL
Volume 103, Issue 9, Pages 1899-1908Publisher
CELL PRESS
DOI: 10.1016/j.bpj.2012.09.025
Keywords
-
Categories
Funding
- National Institutes of Health, Bethesda, Maryland [GM27278]
Ask authors/readers for more resources
Aquaporin-4 (AQP4) is the primary water channel in the mammalian brain, particularly abundant in astrocytes, whose plasma membranes normally contain high concentrations of cholesterol. Here we test the hypothesis that the water permeabilities of two naturally occurring isoforms (AQP4-M1 and AQP4-M23) depend on bilayer mechanical/structural properties modulated by cholesterol and phospholipid composition. Osmotic stress measurements were performed with proteoliposomes containing AQP4 and three different lipid mixtures: 1), phosphatidylcholine (PC) and phosphatidylglycerol (PG); 2), PC, PG, with 40 mol% cholesterol; and 3), sphingomyelin (SM), PG, with 40 mol % cholesterol. The unit permeabilities of AQP4-M1 were 3.3 +/- 0.4 x 10(-13) cm(3)/s (mean +/- SE), 1.2 +/- 0.1 x 10(-13) cm(3)/s, and 0.4 +/- 0.1 x 10(-13) cm(3)/s in PC:PG, PC:PG:cholesterol, and SM:PG:cholesterol, respectively. The unit permeabilities of AQP4-M23 were 2.1 +/- 0.2 x 10(-13) cm(3)/s, 0.8 +/- 0.1 x 10(-13) cm(3)/s, and 0.3 +/- 0.1 x 10(-13) cm(3)/s in PC:PG, PC:PG:cholesterol, and SM:PG:cholesterol, respectively. Thus, for each isoform the unit permeabilities strongly depended on bilayer composition and systematically decreased with increasing bilayer compressibility modulus and bilayer thickness. These observations suggest that altering lipid environment provides a means of regulating water channel permeability. Such permeability changes could have physiological consequences, because AQP4 water permeability would be reduced by its sequestration into SM:cholesterol-enriched raft microdomains. Conversely, under ischemic conditions astrocyte membrane cholesterol content decreases, which could increase AQP4 permeability.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available