期刊
JOURNAL OF CELL BIOLOGY
卷 148, 期 3, 页码 495-504出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.148.3.495
关键词
acidification; polarity; Madin-Darby canine kidney; influenza M2; apical
类别
资金
- NIDDK NIH HHS [R01 DK54407, R01 DK26012, R01 DK054407] Funding Source: Medline
The function of acidification in protein sorting along the biosynthetic pathway has been difficult to elucidate, in part because reagents used to alter organelle pH affect all acidified compartments and are poorly reversible. We have used a novel approach to examine the role of acidification in protein sorting in polarized Madin-Darby canine kidney (MDCK) cells. We expressed the influenza virus M2 protein, an acid-activated ion channel that equilibrates lumenal and cytosolic pH, in polarized MDCK cells and examined the consequences on the targeting and delivery of apical and basolateral proteins. M2 activity affects the pH of only a subset of acidified organelles, and its activity can be rapidly reversed using ion channel blockers (Henkel, J.R., G.Apodaca, Y.Altschuler, S. Hardy, and O.A. Weisz. 1998. Mel. Biol. Cell. 8:2477-2490; Henkel, J.R., J.L. Popovich, G.A.Gibson, S.C. Watkins, and O.A. Weisz. 1999. J. Biol. Chem. 274:9854-9860). M2 expression significantly decreased the kinetics of cell surface delivery of the apical membrane protein influenza hemagglutinin, but not of the basolaterally delivered polymeric immunoglobulin receptor. Similarly, the kinetics of apical secretion of a soluble form of gamma-glutamyl-transpeptidase were reduced with no effect on the basolaterally secreted fraction. Interestingly, M2 activity had no effect on the rate of secretion of a nonglycosylated protein (human growth hormone [hGH]) that was secreted equally from both surfaces. However, M2 slowed apical secretion of a glycosylated mutant of hGH that was secreted predominantly apically. Our results suggest a role for acidic trans-Golgi network pH in signal-mediated loading of apical cargo into forming vesicles.
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