Tang Z, Okamoto T, Boontrakulpoontawee P, Katada T, Otsuka A J, Lisanti M P
The Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142-1479, USA.
J Biol Chem. 1997 Jan 24;272(4):2437-45. doi: 10.1074/jbc.272.4.2437.
Caveolae are vesicular organelles that represent an appendage of the plasma membrane. Caveolin, a 21-24-kDa integral membrane protein, is a principal component of caveolae membranes in vivo. Caveolin has been proposed to function as a plasma membrane scaffolding protein to organize and concentrate signaling molecules within caveolae, including heterotrimeric G proteins (alpha and betagamma subunits). In this regard, caveolin interacts directly with Galpha subunits and can functionally regulate their activity. To date, three cDNAs encoding four subtypes of caveolin have been described in vertebrates. However, evidence for the existence of caveolin proteins in less complex organisms has been lacking. Here, we report the identification, cDNA sequence and genomic organization of the first invertebrate caveolin gene, Cavce (for caveolin from Caenorhabditis elegans). The Cavce gene, located on chromosome IV, consists of two exons interrupted by a 125-nucleotide intron sequence. The region of Cavce that is strictly homologous to mammalian caveolins is encoded by a single exon in Cavce. This suggests that mammalian caveolins may have evolved from the second exon of Cavce. Cavce is roughly equally related to all three known mammalian caveolins and, thus, could represent a common ancestor. Remarkably, the invertebrate Cavce protein behaves like mammalian caveolins: (i) Cavce forms a high molecular mass oligomer, (ii) assumes a cytoplasmic membrane orientation, and (iii) interacts with G proteins. A 20-residue peptide encoding the predicted G protein binding region of Cavce possesses "GDP dissociation inhibitor-like activity" with the same potency as described earlier for mammalian caveolin-1. Thus, caveolin appears to be structurally and functionally conserved from worms to man. In addition, we find that there are at least two caveolin-related genes expressed in C. elegans, defining an invertebrate caveolin gene family. These results establish the nematode C. elegans as an invertebrate model system to study caveolae and caveolin in vivo.
小窝是一种囊泡状细胞器，是质膜的一种附属结构。小窝蛋白是一种21 - 24 kDa的整合膜蛋白，是体内小窝膜的主要成分。有人提出小窝蛋白作为一种质膜支架蛋白，在小窝内组织和聚集信号分子，包括异源三聚体G蛋白（α和βγ亚基）。在这方面，小窝蛋白直接与Gα亚基相互作用，并能在功能上调节其活性。迄今为止，在脊椎动物中已描述了编码小窝蛋白四种亚型的三个cDNA。然而，在不太复杂的生物体中缺乏小窝蛋白存在的证据。在这里，我们报告了第一个无脊椎动物小窝蛋白基因Cavce（来自秀丽隐杆线虫的小窝蛋白）的鉴定、cDNA序列和基因组结构。Cavce基因位于第四条染色体上，由两个外显子组成，中间被一个125个核苷酸的内含子序列打断。Cavce中与哺乳动物小窝蛋白严格同源的区域由Cavce中的一个单一外显子编码。这表明哺乳动物小窝蛋白可能是从Cavce的第二个外显子进化而来的。Cavce与所有三种已知的哺乳动物小窝蛋白的亲缘关系大致相同，因此可能代表一个共同祖先。值得注意的是，无脊椎动物的Cavce蛋白的行为与哺乳动物小窝蛋白相似：（i）Cavce形成高分子量寡聚体，（ii）呈现细胞质膜方向，（iii）与G蛋白相互作用。编码Cavce预测的G蛋白结合区域的一个20个残基的肽具有“GDP解离抑制剂样活性”，其效力与先前描述的哺乳动物小窝蛋白-1相同。因此，从小蠕虫到人类，小窝蛋白在结构和功能上似乎都是保守的。此外，我们发现秀丽隐杆线虫中至少有两个与小窝蛋白相关的基因表达，定义了一个无脊椎动物小窝蛋白基因家族。这些结果确立了线虫秀丽隐杆线虫作为一个在体内研究小窝和小窝蛋白的无脊椎动物模型系统。
