Caveolin-1 is an integral membrane protein of caveolae that is thought to p
lay an important role in both the traffic of cholesterol to caveolae and mo
dulating the activity of multiple signaling molecules at this site. The mol
ecule is synthesized in the endoplasmic reticulum, transported to the cell
surface, and undergoes a poorly understood recycling itinerary. We have use
d mutagenesis to determine the parts of the molecule that control traffic o
f caveolin-1 from its site of synthesis to the cell surface, We identified
four regions of the molecule that appear to influence caveolin-1 traffic, A
region between amino acids 66 and 70, which is in the most conserved regio
n of the molecule, is necessary for exit from the endoplasmic reticulum. Th
e region between amino acids 71 and 80 controls incorporation of caveolin-1
oligomers into detergent-resistant regions of the Golgi apparatus. Amino a
cids 91-100 and 134-154 both control oligomerization and exit from the Golg
i apparatus. Removal of other portions of the molecule has no effect on tar
geting of newly synthesized caveolin-1 to caveolae, The results suggest tha
t movement of caveolin-1 among various endomembrane compartments is control
led at multiple steps.