Expression of Caveolin-1 Is Required for the Transport of Caveolin-2 to the Plasma Membrane

Abstract

Caveolins-1 and -2 are normally co-expressed, and they form a hetero-oligomeric complex in many cell types. These caveolin hetero-oligomers are thought to represent the assembly units that drive caveolae formation in vivo. However, the functional significance of the interaction between caveolins-1 and -2 remains unknown. Here, we show that caveolin-1 co-expression is required for the transport of caveolin-2 from the Golgi complex to the plasma membrane. We identified a human erythroleukemic cell line, K562, that expresses caveolin-2 but fails to express detectable levels of caveolin-1. This allowed us to stringently assess the effects of recombinant caveolin-1 expression on the behavior of endogenous caveolin-2. We show that expression of caveolin-1 in K562 cells is sufficient to reconstitute the de novo formation of caveolae in these cells. In addition, recombinant expression of caveolin-1 allows caveolin-2 to form high molecular mass oligomers that are targeted to caveolae-enriched membrane fractions. In striking contrast, in the absence of caveolin-1 expression, caveolin-2 forms low molecular mass oligomers that are retained at the level of the Golgi complex. Interestingly, we also show that expression of caveolin-1 in K562 cells dramatically up-regulates the expression of endogenous caveolin-2. Northern blot analysis reveals that caveolin-2 mRNA levels remain constant under these conditions, suggesting that the expression of caveolin-1 stabilizes the caveolin-2 protein. Conversely, transient expression of caveolin-2 in CHO cells is sufficient to up-regulate endogenous caveolin-1 expression. Thus, the formation of a hetero-oligomeric complex between caveolins-1 and -2 stabilizes the caveolin-2 protein product and allows caveolin-2 to be transported from the Golgi complex to the plasma membrane.

Differences in Caveolae Dynamics in Vascular Smooth Muscle Cells of Different Phenotypes

“…Caveolin-2 showed weaker immunoreactivity, which was mainly found in Golgi elements both in contractile and synthetic cells. This agrees with recent reports showing that caveolin-1 and -2 are co-expressed in many cells (Scherer et al, 1997) and that caveolin-2 is localized in Golgi but redistributes to caveolae when co-expressed with caveolin-1 Parolini et al, 1999). The third isoform, caveolin-3, primarily occurs in skeletal and heart muscle cells, but smaller amounts are also found in smooth muscle cells (Song et al, 1996).…”

Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue

“…Caveolin-1 and -2 form a functional heterooligomeric complex in cells where they are coexpressed (36). Caveolin-2 requires coexpression with caveolin-1; in the absence of caveolin-1, caveolin-2 remains trapped in the Golgi complex and undergoes proteasomal degradation (24). Therefore, all of the phenotypes identified in the Cav-1-null mouse must also be examined in the Cav-2-null mouse to determine whether the findings are due to a functional caveolin-2 deficiency.…”

Arachidonic Acid Release from Mammalian Cells Transfected with Human Groups IIA and X Secreted Phospholipase A2 Occurs Predominantly during the Secretory Process and with the Involvement of Cytosolic Phospholipase A2-α

“…44 -48). Some caveolin-2 is found in caveolae, in association with caveolin-1, but even in these cases, most of the caveolin-2 detected by immunofluorescence resides in the Golgi complex (45)(46)(47). A recent study showed co-localization of human group V sPLA 2 with caveolin-2 in punctate domains in the macrophage-like cell line p388D1 (49).…”