CDNA CLONING AND CHARACTERIZATION OF LAMINA-ASSOCIATED POLYPEPTIDE 1C (LAP1C), AN INTEGRAL PROTEIN OF THE INNER NUCLEAR-MEMBRANE

CDNA CLONING AND CHARACTERIZATION OF LAMINA-ASSOCIATED POLYPEPTIDE 1C (LAP1C), AN INTEGRAL PROTEIN OF THE INNER NUCLEAR-MEMBRANE
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DOI:
10.1074/jbc.270.15.8822
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发表时间:
1995-04-14
影响因子:
4.8
通讯作者:
GERACE, L
GERACE, L
中科院分区:
生物学2区
文献类型:
--
作者:
MARTIN, L;CRIMAUDO, C;GERACE, L

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板层相关多肽1A-1C(LAPs1A-1C)是核内膜上与A型和B型板层结合的相关膜蛋白,在核板膜的附着和组装中起重要作用。在本研究中,我们克隆了LAP1C的编码基因。DNA序列预测了一个由506个氨基酸组成的蛋白质,具有很大的亲水性,在残基311-333之间有一个单一的跨膜区域。对抗LAP1单抗RL13识别的表位的定位表明,含有残基1-310的亲水区暴露在核质中,因此LAP1C是一种II型完整膜蛋白。分离到第二类LAP1cDNAs,在LAP1C序列中含有两个编码核苷酸的蛋白质插入。这些基因可能编码部分LAPs1A和/或-1B,提示LAP1亚型来自选择性剪接。对小鼠P19畸胎癌细胞及其P19MES分化衍生物的免疫印迹分析表明,LAP1亚型在发育过程中存在差异表达,类似于核层粘连蛋白家族的成员。由于不同的LAP1亚型似乎与具有不同亲和力的层结合在一起,这些表达的变化可能对核结构的发育调节变化很重要。
Lamina-associated polypeptides 1A-1C (LAPs1A-1C) are related integral membrane proteins of the inner nuclear membrane that bind to both A- and B-type lamins and have a putative role in the membrane attachment and assembly of the nuclear lamina. In this study, we have cloned a cDNA encoding LAP1C. The DNA sequence predicts a 506-amino acid protein of largely hydrophilic character with a single membrane-spanning region between residues 311-333. Mapping of the epitope recognized by the anti-LAP1 monoclonal antibody RL13 indicates that the hydrophilic domain containing residues 1-310 is exposed to the nucleoplasm and thus that LAP1C is a type II integral membrane protein. A second class of LAP1 cDNAs was isolated that contains two protein coding nucleotide insertions in the LAP1C sequence. These probably encode parts of LAPs1A and/or -1B, suggesting that LAP1 isotypes arise from alternative splicing. Immunoblot analysis of mouse P19 teratocarcinoma cells and the P19MES-differentiated derivative of the latter suggest that LAP1 isotypes are differentially expressed during development, similar to members of the nuclear lamin family. Since the different LAP1 isotypes appear to bind lamins with different affinities, these changes in expression could be important for developmentally regulated alterations in nuclear structure.