PMID: 11335105May 4, 2001Paper

Glycation decreases calmodulin binding to lens transmembrane protein, MIP

Biochimica Et Biophysica Acta
S Swamy-Mruthinti

Abstract

Channels of the major intrinsic protein (MIP) of the lens transport water, thus playing an important role in lens fiber cell homeostasis. Calmodulin (CAM) interacts with MIP and possibly regulates MIP channel permeability. Protein glycation has been implicated in lens opacification. We previously identified sites of glycation of MIP, which are in close proximity to the putative CAM binding site. This study is aimed to show the effect of in vitro and in vivo glycation on CAM binding to MIP. Our results show that MIP and MP20 are the major CAM binding proteins of the lens membrane. In vitro incubation of lens membranes with 1 M glucose decreased CAM binding by 38% (P<0.001). Similarly, there was a progressive decrease in CAM binding to diabetic lens membranes compared to age-matched controls (up to 30% decrease, P<0.01). Mutation of K228 and K238 as well as a triple K mutation (K228N, K238N, K259N) of MIP resulted in a decrease in CAM binding. Thus, post-translational protein modifications of MIP influence CAM binding. Since CAM is the ubiquitous Ca(2+) receptor, decreases in CAM binding to the target protein will affect the Ca(2+)-mediated cellular processes leading to lens opacification in diabetic and aging lenses.

References

Sep 1, 1992·Current Eye Research·M S Swamy, E C Abraham
May 1, 1990·Experimental Eye Research·C F LouisG Strasburg
Apr 1, 1981·Experimental Eye Research·P RussellJ H Kinoshita
Mar 1, 1994·Current Eye Research·J SandersonG Duncan
Oct 1, 1993·Current Eye Research·A Shiels, C S Griffin
Sep 1, 1997·Current Eye Research·S Swamy-Mruthinti, K L Schey

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Citations

Apr 14, 2004·The Journal of General Physiology·Karin L Németh-CahalanJames E Hall
Apr 16, 2009·Cell Biochemistry and Function·José NicolauMarcela Carrilho
Nov 5, 2003·Journal of Experimental Zoology. Part A, Comparative Experimental Biology·Ana B Chepelinsky
Nov 28, 2012·Proteomics. Clinical Applications·Mahesh J KulkarniAshok P Giri
Jan 2, 2008·Journal of Molecular Biology·Tamir GonenThomas Walz
Apr 23, 2011·Biochimica Et Biophysica Acta·S Sindhu KumariKulandaiappan Varadaraj

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