Kirkham Matthew, Nixon Susan J, Howes Mark T, Abi-Rached Laurent, Wakeham Diane E, Hanzal-Bayer Michael, Ferguson Charles, Hill Michelle M, Fernandez-Rojo Manuel, Brown Deborah A, Hancock John F, Brodsky Frances M, Parton Robert G
Institute for Molecular Bioscience, University of Queensland, Queensland, Brisbane, Australia.
J Cell Sci. 2008 Jun 15;121(Pt 12):2075-86. doi: 10.1242/jcs.024588. Epub 2008 May 27.
Caveolae are an abundant feature of mammalian cells. Integral membrane proteins called caveolins drive the formation of caveolae but the precise mechanisms underlying caveola formation, and the origin of caveolae and caveolins during evolution, are unknown. Systematic evolutionary analysis shows conservation of genes encoding caveolins in metazoans. We provide evidence for extensive and ancient, local and genomic gene duplication, and classify distinct caveolin gene families. Vertebrate caveolin-1 and caveolin-3 isoforms, as well as an invertebrate (Apis mellifera, honeybee) caveolin, all form morphologically identical caveolae in caveolin-1-null mouse cells, demonstrating that caveola formation is a conserved feature of evolutionarily distant caveolins. However, coexpression of flotillin-1 and flotillin-2 did not cause caveola biogenesis in this system. In contrast to the other tested caveolins, C. elegans caveolin is efficiently transported to the plasma membrane but does not generate caveolae, providing evidence of diversity of function in the caveolin gene family. Using C. elegans caveolin as a template to generate hybrid caveolin constructs we now define domains of caveolin required for caveolae biogenesis. These studies lead to a model for caveola formation and novel insights into the evolution of caveolin function.
小窝是哺乳动物细胞的一个显著特征。称为小窝蛋白的整合膜蛋白驱动小窝的形成，但小窝形成的精确机制以及小窝和小窝蛋白在进化过程中的起源尚不清楚。系统进化分析表明后生动物中编码小窝蛋白的基因具有保守性。我们提供了广泛而古老的、局部和基因组基因复制的证据，并对不同的小窝蛋白基因家族进行了分类。脊椎动物的小窝蛋白-1和小窝蛋白-3亚型，以及一种无脊椎动物（蜜蜂，Apis mellifera）的小窝蛋白，在缺乏小窝蛋白-1的小鼠细胞中均形成形态相同的小窝，这表明小窝形成是进化上远缘的小窝蛋白的一个保守特征。然而，在该系统中，共表达浮舰蛋白-1和浮舰蛋白-2并不会导致小窝的生物发生。与其他测试的小窝蛋白不同，秀丽隐杆线虫的小窝蛋白能有效地转运到质膜，但不会产生小窝，这为小窝蛋白基因家族功能的多样性提供了证据。利用秀丽隐杆线虫的小窝蛋白作为模板生成杂交小窝蛋白构建体，我们现在确定了小窝生物发生所需的小窝蛋白结构域。这些研究得出了一个小窝形成模型，并对小窝蛋白功能的进化有了新的认识。
