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Proceedings of the …

Caveolin, a 21to 24-kDa integral membrane protein, is a principal component of caveolae membranes... more Caveolin, a 21to 24-kDa integral membrane protein, is a principal component of caveolae membranes. Caveolin interacts directly with heterotrimeric guanine nucleotide binding proteins (G proteins) and can functionally regulate their activity. Here, an 20-kDa caveolin-related protein, caveolin-2, was identified through microsequencing of adipocyte-derived caveolin-enriched membranes; caveolin was retermed caveolin-1. Caveolins 1 and 2 are similar in most respects. mRNAs for both caveolin-1 and caveolin-2 are most abundantly expressed in white adipose tissue and are induced during adipocyte differentiation. Caveolin-2 colocalizes with caveolin-1, indicating that caveolin-2 also localizes to caveolae. However, caveolin-1 and caveolin-2 differ in their functional interactions with heterotrimeric G proteins, possibly explaining why caveolin-1 and-2 are coexpressed within a single cell. Caveolae are plasma membrane specializations present in most cell types (1). They are most conspicuous in adipocytes were they represent up to 20% of the total plasma membrane surface area (2). Cytoplasmically oriented signaling molecules are concentrated within these structures, including heterotrimeric guanine nucleotide binding proteins (G proteins), Srclike kinases, protein kinase Ca and Ras-related GTPases (3-9). The caveolae signaling hypothesis states that caveolar localization of signaling molecules could provide a compartmental basis for integrating certain transmembrane signaling events (1). Caveolin, a 21to 24-kDa integral membrane protein, is the main component of caveolae membranes (10). Structurally, caveolin can be divided into three distinct regions: a hydrophilic cytosolic N-terminal domain, a membranespanning region, and a hydrophilic C-terminal domain (11). The C-terminal domain undergoes palmitoylation (Sacylation) on three cysteine residues (12), suggesting that both the membrane-spanning region and the C-terminal domain of caveolin are associated with the membrane. Recent evidence suggests that caveolin may function as a scaffolding protein for organizing and concentrating certain caveolin-interacting molecules within caveolae membranes (3, 13). Although caveolin is the product of a single gene, it encodes one mRNA but two caveolin isoforms that differ by 3 kDa and have been termed a-and ,B-caveolin (14). a-caveolin contains residues 1-178; methionine 32 acts as an internal translation initiation site to form ,B-caveolin (14). Both caveolin isoforms are targeted to caveolae (15), form homooligomers (16, 17), and interact with G proteins (13). However, a-and ,B-caveolin assume a distinct but overlapping subcellular distribution in intact cells (14) and only ,B-caveolin is phosphorylated on serine residues in vivo (15). These results suggest The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

Proceedings of the …

Caveolin, a 21to 24-kDa integral membrane protein, is a principal component of caveolae membranes... more Caveolin, a 21to 24-kDa integral membrane protein, is a principal component of caveolae membranes. Caveolin interacts directly with heterotrimeric guanine nucleotide binding proteins (G proteins) and can functionally regulate their activity. Here, an 20-kDa caveolin-related protein, caveolin-2, was identified through microsequencing of adipocyte-derived caveolin-enriched membranes; caveolin was retermed caveolin-1. Caveolins 1 and 2 are similar in most respects. mRNAs for both caveolin-1 and caveolin-2 are most abundantly expressed in white adipose tissue and are induced during adipocyte differentiation. Caveolin-2 colocalizes with caveolin-1, indicating that caveolin-2 also localizes to caveolae. However, caveolin-1 and caveolin-2 differ in their functional interactions with heterotrimeric G proteins, possibly explaining why caveolin-1 and-2 are coexpressed within a single cell. Caveolae are plasma membrane specializations present in most cell types (1). They are most conspicuous in adipocytes were they represent up to 20% of the total plasma membrane surface area (2). Cytoplasmically oriented signaling molecules are concentrated within these structures, including heterotrimeric guanine nucleotide binding proteins (G proteins), Srclike kinases, protein kinase Ca and Ras-related GTPases (3-9). The caveolae signaling hypothesis states that caveolar localization of signaling molecules could provide a compartmental basis for integrating certain transmembrane signaling events (1). Caveolin, a 21to 24-kDa integral membrane protein, is the main component of caveolae membranes (10). Structurally, caveolin can be divided into three distinct regions: a hydrophilic cytosolic N-terminal domain, a membranespanning region, and a hydrophilic C-terminal domain (11). The C-terminal domain undergoes palmitoylation (Sacylation) on three cysteine residues (12), suggesting that both the membrane-spanning region and the C-terminal domain of caveolin are associated with the membrane. Recent evidence suggests that caveolin may function as a scaffolding protein for organizing and concentrating certain caveolin-interacting molecules within caveolae membranes (3, 13). Although caveolin is the product of a single gene, it encodes one mRNA but two caveolin isoforms that differ by 3 kDa and have been termed a-and ,B-caveolin (14). a-caveolin contains residues 1-178; methionine 32 acts as an internal translation initiation site to form ,B-caveolin (14). Both caveolin isoforms are targeted to caveolae (15), form homooligomers (16, 17), and interact with G proteins (13). However, a-and ,B-caveolin assume a distinct but overlapping subcellular distribution in intact cells (14) and only ,B-caveolin is phosphorylated on serine residues in vivo (15). These results suggest The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.