Function of the tetraspanin CD151-α6β1 integrin complex during cellular morphogenesis
Function of the tetraspanin CD151-α6β1 integrin complex during cellular morphogenesis
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DOI：
10.1091/mbc.01-10-0481
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发表时间：
2002-01-01
影响因子：
3.3
通讯作者：
Hemler, ME
中科院分区：
文献类型：
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作者：
Zhang, XA;Kazarov, AR;Hemler, ME
NIH3T3细胞在基底膜Matrigel上镀后，形成绳状结构的吻合网络，可被抗α 6beta1整合素抗体抑制。对于转染了人CD151蛋白的NIH3T3细胞，抗CD151抗体也能抑制绳状网络的形成。此外，CD151和alpha6beta1在NIH3T3细胞中存在物理关联。当CD151短的8个氨基酸c末端尾部被移除（通过删除或交换）时，外源CD151发挥了主要的负面作用，因为它几乎完全抑制了依赖alpha6beta1的细胞网络的形成和NIH3T3细胞在laminin-1（一种alpha6beta1配体）上的扩散。重要的是，突变型CD151保留了alpha6beta1的关联，并且没有改变alpha6beta1介导的细胞对Matrigel的粘附。总之，CD151-alpha6beta1整合素复合物作为一个功能单元，显著影响细胞形态发生，其中CD151尾部在确定配体结合后alpha6beta1整合素的“由外而内”功能方面尤为重要。此外，针对alpha6beta1和CD151的抗体抑制内皮细胞索样网络的形成，从而指出CD151-alpha6beta1复合物在血管生成过程中可能存在相关性。
Upon plating on basement membrane Matrigel, NIH3T3 cells formed an anastomosing network of cord-like structures, inhibitable by anti-alpha6beta1 integrin antibodies. For NIH3T3 cells transfected with human CD151 protein, the formation of a cord-like network was also inhibitable by anti-CD151 antibodies. Furthermore, CD151 and alpha6beta1 were physically associated within NIH3T3 cells. On removal of the short 8-amino acid C-terminal CD151 tail (by deletion or exchange), exogenous CD151 exerted a dominant negative effect, as it almost completely suppressed alpha6beta1-dependent cell network formation and NIH3T3 cell spreading on laminin-1 (an alpha6beta1 ligand). Importantly, mutant CD151 retained alpha6beta1 association and did not alter alpha6beta1-mediated cell adhesion to Matrigel. In conclusion, the CD151-alpha6beta1 integrin complex acts as a functional unit that markedly influences cellular morphogenesis, with the CD151 tail being of particular importance in determining the "outside-in" functions of alpha6beta1-integrin that follow ligand engagement. Also, antibodies to alpha6beta1 and CD151 inhibited formation of endothelial cell cord-like networks, thus pointing to possible relevance of CD151-alpha6beta1 complexes during angiogenesis.