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Traffic. 2000 Apr;1(4):326-41.

Role of cholesterol in developing T-tubules: analogous mechanisms for T-tubule and caveolae biogenesis.

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Centre for Microscopy and Microanalysis, Department of Physiology and Pharmacology and Centre for Molecular and Cellular Biology, University of Queensland, Queensland, 4072, Australia.


Recent work has suggested that caveolae biogenesis and transverse-tubule (T-tubule) formation in muscle cells share similar underlying features. We compared the properties of caveolin-1 (cav-1)-positive caveolae, in epithelial cells, with caveolin-3 (cav-3)-positive precursor T-tubules, in differentiating C2C12 muscle cells, using the cholesterol-binding drug, Amphotericin B (AmphB). Treatment of MDCK epithelial cells with acute high doses or chronic low doses of AmphB caused a loss of surface caveolae and the rapid redistribution of cav-1, and exogenously expressed cav-3, from the cell surface into modified endosomes. This effect was reversible and specific, as the GPI-anchored protein, alkaline phosphatase, was largely unaffected by the treatment unless it had been previously partitioned into caveolar domains. In differentiating C2C12 mouse myotubes, AmphB also caused a complete redistribution of cav-3 from precursor T-tubule elements into enlarged endosomes, morphologically very similar to those seen in MDCK cells. This was accompanied by redistribution of a T-tubule marker and a dramatic reduction in the extent of surface-connected tubular elements. We propose that cholesterol-enriched glycolipid 'raft' domains are involved in the formation and maintenance of diverse membrane systems including caveolae and the T-tubule system of muscle.

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