Chromosomal localization, genomic organization, and developmental expression of the murine caveolin gene family (Cav-1, -2, and -3) - Cav-1 and Cav-2 genes map to a known tumor suppressor locus (6-A2/731)
Chromosomal localization, genomic organization, and developmental expression of the murine caveolin gene family (Cav-1, -2, and -3) - Cav-1 and Cav-2 genes map to a known tumor suppressor locus (6-A2/731)
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DOI：
10.1016/s0014-5793(98)00619-x
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发表时间：
1998-06-16
期刊：
影响因子：
3.5
通讯作者：
Lisanti, MP
中科院分区：
文献类型：
--
作者：
Engelman, JA;Zhang, XL;Lisanti, MP
卡雷奥林斯（Cav-1、-2和-3）是细胞质膜锚定支架蛋白的基因家族，其：（i）帮助从质膜适当地雕刻小窝膜;和（ii）参与无活性信号分子的隔离。在成人中，小窝蛋白-1和-2共表达，并且在I型肺细胞、内皮细胞、成纤维细胞和脂肪细胞中最丰富，虽然caveolin-3的表达仅限于横纹肌细胞，但是关于caveolin基因家族的基因组结构和发育表达知之甚少。在此，我们以小鼠为模型系统，研究了caveolin基因家族的染色体定位、详细的内含子-外显子结构和发育表达模式，并以编码caveolin-1、-2和-3的cDNA为探针分离了含有这些基因的小鼠基因组克隆，使用这些基因组克隆作为探针的荧光原位杂交（FISH）分析显示，所有三个小窝蛋白基因都定位于小鼠6号染色体，具体地，小窝蛋白-1和小窝蛋白-2共定位于染色体区域6-A2，而小窝蛋白-3位于染色体区域6-E1内。NCBI人/小鼠同源性图谱显示鼠区域6-A2对应于人染色体7 q31。由于该区域（6-A2/7 q31）是一个尚未确定的肿瘤抑制基因的位点，我们的定位研究明确地将小窝蛋白-1和小窝蛋白-2确定为可能在这些位点缺失的候选基因。所有三个小窝蛋白基因显示出相似的内含子-外显子组织，每个基因的最后一个外显子编码大部分已知的小窝蛋白功能结构域。最后一个外显子的边界位置在所有三个小窝蛋白基因中基本上是相同的，这表明它们可能是通过基因复制事件产生的。发育上，所有三个小窝蛋白在小鼠胚胎发育后期表达，如通过北方和Western印迹分析所评估的。我们使用一组充分表征的抗体探针检测了d16小鼠胚胎切片中小窝蛋白的定位，小窝蛋白-1和-2在发育中的肺实质中表达最丰富，而小窝蛋白-3在主要由骨骼肌细胞组成的发育中的组织中表达最丰富。尽管所有三种小窝蛋白在成体中的表达在终末分化的细胞类型中最高，但这与小窝蛋白可被视为胚胎发生期间分化的晚期标志物的观点一致。(C)1998年欧洲生物化学学会联合会。
Careolins (Cav-1, -2, and -3) are a gene family of cytoplasmic membrane-anchored scaffolding proteins that: (i) help to sculpt caveolae membranes from the plasma membrane proper; and (ii) participate in the sequestration of inactive signaling molecules, In the adult, caveolin-1 and -2 are coexpressed and are most abundant in type I pneumocytes, endothelia, fibroblastic cells and adipocytes, while the expression of caveolin-3 is restricted to striated muscle cells, However, little is known regarding the genomic organization and developmental expression of the caveolin gene family. Here, using the mouse as a model system, we examine the chromosomal localization, the detailed intron-exon organization, and developmental expression pattern of the caveolin gene family, cDNAs encoding caveolin-1, -2, and -3 were used as probes to isolate murine genomic clones containing these genes, Fluorescence in situ hybridization (FISH) analysis using these genomic clones as probes reveals that all three caveolin genes are localized to murine chromosome 6, Specifically, caveolin-1 and -2 co-localize to chromosomal region 6-A2, while caveolin-3 is located within the chromosomal region 6-E1, Searches of the NCBI Human/Mouse Homology map indicate that murine region 6-A2 corresponds to human chromosome 7q31. As this region (6-A2/7q31) is the site of an as Set unidentified tumor suppressor gene(s), our mapping studies clearly define caveolin-1 and caveolin-2 as candidate genes that may de deleted at these loci. All three caveolin genes show similar intron-exon organization, with the last exon of each gene encoding the bulk of the known caveolin functional domains. The boundary position of the last exon is essentially identical in all three caveolin genes, suggesting that they may have arisen through gene duplication events, Developmentally, all three caveolins were expressed late during mouse embryogenesis as assessed by Northern and Western blot analysis. We examined the localization of the caveolin proteins in Sections of da 16 mouse embryos using a well-characterized panel of antibody probes, Caveolin-1 and -2 were most abundantly expressed in the developing lung parenchyma, while caveolin-3 was most abundantly expressed in developing tissues that consist primarily of skeletal muscle cells. ris the expression of all three caveolins in the adult is highest in terminally differentiated cell types, this is consistent with the idea that caveolins may be viewed as late markers of differentiation during embryogenesis. (C) 1998 Federation of European Biochemical Societies.