Disease linked to cell traffic jamsJun. 20, 2013, 8:00 AM
The protein caveolin-1 is an essential part of caveolae – small folded-in “pockets” of the cell membrane that have roles in multiple cellular processes. Mutations in caveolin-1 – and changes in its expression levels – have been linked to a number of human diseases, and mutant caveolins appear to accumulate inside the cell.
To explore why caveolin-1 is trapped inside the cell, Anne Kenworthy, Ph.D., associate professor of Molecular Physiology and Biophysics, and colleagues compared a breast cancer-associated mutant caveolin-1 and wild-type caveolin-1, both “tagged” with a fluorescent marker. They were surprised to find that the overexpressed wild-type caveolin-1 mimicked the behavior of the mutant and accumulated inside the cell. They report in the June issue of the journal Traffic that the type of marker “tag” and the cellular context both affect the distribution of caveolin-1. They also identified conformational changes associated with incorrectly targeted forms of the protein.
The findings raise the possibility that common trafficking defects underlie diseases associated with both overexpression of and mutations in caveolin-1.
This research was supported by grants from the National Institutes of Health (GM073846, HL111259).