The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes.
The structures of the human calcium channel alpha 1 subunit (CACNL1A2) and beta subunit (CACNLB3) genes.
复制标题
人钙通道 α 1 亚基 (CACNL1A2) 和 β 亚基 (CACNLB3) 基因的结构。
DOI：
10.1006/geno.1995.1048
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发表时间：
1995
期刊：
影响因子：
4.4
通讯作者：
Y. Seino
中科院分区：
文献类型：
--
作者：
Y. Yamada;K. Masuda;Q. Li;Y. Ihara;A. Kubota;T. Miura;K. Nakamura;Y. Fujii;S. Seino;Y. Seino
胰腺β细胞中的钙内流主要由L型电压依赖性钙通道（VDCCs）调节并触发胰岛素分泌。VDCC的α 1亚基（CACN 4）和β亚基（β 3）均在胰岛中表达，是VDCC活性的主要组分，因此它们可能在胰岛素分泌的调节中发挥关键作用。我们已经确定了人类CACN 4（CACNL 1A 2）和人类β 3（CACNLB 3）基因的结构。CACNL 1A 2基因全长超过155 kb，有49个外显子。大多数被内含子中断的位置在CACNL 1A 2基因和先前报道的L型VDCC α 1亚基CACNL 1A 1基因之间是很保守的。另一方面，CACNLB 3基因分布在约8 kb内，包含13个外显子，其中大部分外显子一起位于约5 kb内。CACNL 1A 2基因组序列与先前报道的cDNA序列的比较表明，在人类CACNL 1A 2基因中存在许多多态性。此外，CACNL 1A 2的外显子1的PCR-SSCP程序揭示了从7到8个ATG三核苷酸重复的非胰岛素依赖型糖尿病（NIDDM）患者的变化，导致在CACN 4的氨基末端的甲硫氨酸的增加。人CACNL 1A 2和CACNLB 3基因结构的确定将有助于研究这些基因在NIDDM和其他遗传性疾病如长QT综合征的发展中的作用。
Calcium influx in pancreatic beta-cells is regulated mainly by L-type voltage-dependent calcium channels (VDCCs) and triggers insulin secretion. The alpha 1 subunit (CACN4) and the beta subunit (beta 3) of VDCCs, both of which are expressed in pancreatic islets, are major components for the VDCC activity, and so they may play a critical role in the regulation of insulin secretion. We have determined the structures of the human CACN4 (CACNL1A2) and the human beta 3 (CACNLB3) genes. The CACNL1A2 gene spans more than 155 kb and has 49 exons. Most of the positions interrupted by introns are well conserved between the CACNL1A2 gene and the previously reported L-type VDCC alpha 1 subunit, CACNL1A1, gene. On the other hand, the CACNLB3 gene distributes in approximately 8 kb and comprises 13 exons, most of which are located together within approximately 5 kb. Comparisons of the genomic sequences of CACNL1A2 with the previously reported cDNA sequences indicate that there are a number of polymorphisms in the human CACNL1A2 gene. In addition, the PCR-SSCP procedure of exon 1 of CACNL1A2 revealed a change from 7 to 8 ATG trinucleotide repeats in a patient with non-insulin-dependent diabetes mellitus (NIDDM), resulting in an addition of methionine at the amino-terminus of CACN4. The determination of the structures of the human CACNL1A2 and CACNLB3 genes should facilitate study of the role of these genes in the development of NIDDM and also other genetic diseases such as long QT syndrome.