Abstract. We have studied the biosynthesis and transport of the endogenous caveolins in MDCK cells. We show that in addition to homooligomers of caveolin-1, heterooligomeric complexes of caveolin-1 and -2 are formed in the ER. The oligomers become larger, increasingly detergent insoluble, and phosphorylated on caveolin-2 during transport to the cell surface. In the TGN caveolin-1/-2 heterooligomers are sorted into basolateral vesicles, whereas larger caveolin-1 homooligomers are targeted to the apical side. Caveolin-1 is present on both the apical and basolateral plasma membrane, whereas caveolin-2 is enriched on the basolateral surface where caveolae are present. This suggests that caveolin-1 and -2 heterooligomers are involved in caveolar biogenesis in the basolateral plasma membrane. Anti–caveolin-1 antibodies inhibit the apical delivery of influenza virus hemagglutinin without affecting basolateral transport of vesicular stomatitis virus G protein. Thus, we suggest that caveolin-1 homooligomers play a role in apical transport.
Caveolin-1 and -2 in the Exocytic Pathway of MDCK Cells
We thank members of the Simons lab for critical support, K. Ekroos and S. Brendel for expert technical assistance, W. Huttner (Universität Heidelberg, Heidelberg, Germany) for a critical reading of the manuscript, K. Ashman for peptide sequencing, M. Zerial for the λZAP library, J. Lanoix for rat liver cytosol, S. Bhakdi (Universität Mainz) for the generous supply of SLO, A. Puolasmaa (MSD-Finland) for the kind gift of lovastatin, and Anton G. Rietveld (European Molecular Biology Laboratory) for the help with cholesterol determinations.
This work was financially supported by the Academy of Finland, Commission of the European Communities, Theleton, and SFB 352.
E. Ikonen's present address is Dept. of Biochemistry, National Public Health Institute, Mannerheimintie 166, FIN-00300 Helsinki, Finland.
Address all correspondence to K. Simons, Cell Biology Programme, European Molecular Biology Laboratory, Meyerhofstrasse 1, Postfach 10 2209, D-69012 Heidelberg, Germany. Tel.: (49) 622-138-7334. Fax: (49) 622-138-7512.
1. Abbreviations used in this paper: 2D, two-dimensional; HA, influenza virus hemagglutinin; SLO, streptolysin-O; VSV-G, vesicular stomatitis virus glycoprotein.
P. Scheiffele, P. Verkade, A.M. Fra, H. Virta, K. Simons, E. Ikonen; Caveolin-1 and -2 in the Exocytic Pathway of MDCK Cells . J Cell Biol 23 February 1998; 140 (4): 795–806. doi: https://doi.org/10.1083/jcb.140.4.795
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