The localization of bullous pemphigoid antigen 180 (BP180) in hemidesmosomes is mediated by its cytoplasmic domain and seems to be regulated by the beta4 integrin subunit.
The localization of bullous pemphigoid antigen 180 (BP180) in hemidesmosomes is mediated by its cytoplasmic domain and seems to be regulated by the beta4 integrin subunit.
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DOI：
10.1083/jcb.136.6.1333
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发表时间：
1997-03-24
影响因子：
7.8
通讯作者：
Sonnenberg, A
中科院分区：
文献类型：
--
作者：
Borradori, L;Koch, PJ;Niessen, CM;Erkeland, S;vanLeusden, MR;Sonnenberg, A
大疱性类天疱疮抗原180（BP 180）是半桥粒的组分，即，细胞-基质粘附复合物为了确定BP 180的特定序列对其在半桥粒中的掺入的功能，我们用编码野生型和缺失突变形式的人BP 180的cDNA构建体转染了804 G细胞。结果表明，BP 180的胞质结构域包含足够的信息，用于将蛋白质募集到半桥粒中，因为细胞外和跨膜结构域的去除不会消除靶向。嵌合蛋白的表达，其中包括融合到BP 180的胞质结构域的K-Ras的膜靶向序列，增加内部缺失或缺乏NH 2末端，表明BP 180在半桥粒中的定位是由跨越265个氨基酸的片段介导的。该区段包括位于BP 180的胞质结构域的中心部分内和NH 2末端的两个重要区域。为了研究α6β4整联蛋白对BP 180亚细胞分布的影响，我们用BP 180以及人α 6 A和β4的cDNA转染了缺乏α6β4和BP 180的COS-7细胞。我们提供的证据表明，缺乏胶原胞外结构域的BP 180突变体以及含有BP 180整个胞质结构域的嵌合蛋白与α6β4共定位。相反，当用α 6 A和β4突变体的cDNA转染细胞时，无论是缺乏胞质COOH末端的一半还是在胞质结构域的酪氨酸激活基序中携带苯丙氨酸取代，重组BP 180分子大多数不与α6β4共定位，但仍然弥散分布在细胞表面。此外，在用α 6 A和β4/β1嵌合体的cDNA转染的细胞中，其中β4的胞质结构域被β1整联蛋白亚基的胞质结构域取代，BP 180在粘着斑中不与α6β4/β1嵌合体共定位，而是仍然弥散分布。这些结果表明，β4胞质结构域内的序列决定了BP 180的亚细胞分布。
Bullous pemphigoid antigen 180 (BP180) is a component of hemidesmosomes, i.e., cell-substrate adhesion complexes. To determine the function of specific sequences of BP180 to its incorporation in hemidesmosomes, we have transfected 804G cells with cDNA-constructs encoding wild-type and deletion mutant forms of human BP180. The results show that the cytoplasmic domain of BP180 contains sufficient information for the recruitment of the protein into hemidesmosomes because removal of the extracellular and transmembrane domains does not abolish targeting. Expression of chimeric proteins, which consist of the membrane targeting sequence of K-Ras fused to the cytoplasmic domain of BP180 with increasing internal deletions or lacking the NH2 terminus, indicates that the localization of BP180 in hemidesmosomes is mediated by a segment that spans 265 amino acids. This segment comprises two important regions located within the central part and at the NH2 terminus of the cytoplasmic domain of BP180. To investigate the effect of the α6β4 integrin on the subcellular distribution of BP180, we have transfected COS-7 cells, which lack α6β4 and BP180, with cDNAs for BP180 as well as for human α6A and β4. We provide evidence that a mutant form of BP180 lacking the collagenous extracellular domain as well as a chimeric protein, which contains the entire cytoplasmic domain of BP180, are colocalized with α6β4. In contrast, when cells were transfected with cDNAs for α6A and mutant forms of β4, either lacking the cytoplasmic COOH-terminal half or carrying phenylalanine substitutions in the tyrosine activation motif of the cytoplasmic domain, the recombinant BP180 molecules were mostly not colocalized with α6β4, but remained diffusely distributed at the cell surface. Moreover, in cells transfected with cDNAs for α6A and a β4/β1 chimera, in which the cytoplasmic domain of β4 was replaced by that of the β1 integrin subunit, BP180 was not colocalized with the α6β4/β1 chimera in focal adhesions, but remained again diffusely distributed. These results indicate that sequences within the cytoplasmic domain of β4 determine the subcellular distribution of BP180.
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影响因子：
7.5
作者：
Borradori, L;Sonnenberg, A
通讯作者：
Sonnenberg, A
影响因子：
11.4
作者：
HOGERVORST, F;KUIKMAN, I;SONNENBERG, A
通讯作者：
SONNENBERG, A
影响因子：
6.5
作者：
HOPKINSON, SB;RIDDELLE, KS;JONES, JCR
通讯作者：
JONES, JCR
影响因子：
14.9
作者：
HUANG, MTF;GORMAN, CM
通讯作者：
GORMAN, CM
Alpha 6β4整合素的表面迁移和在伤口愈合模型中的半底体组装。
影响因子：
7.8
作者：
Kurpakus, M A;Quaranta, V;Jones, J C
通讯作者：
Jones, J C