The membrane-cytoplasm interface of integrin alpha subunits is critical for receptor latency
The membrane-cytoplasm interface of integrin alpha subunits is critical for receptor latency
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DOI：
10.1091/mbc.7.10.1499
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发表时间：
1996-10-01
影响因子：
3.3
通讯作者：
Marcantonio, EE
中科院分区：
文献类型：
--
作者：
Briesewitz, R;Kern, A;Marcantonio, EE
在配体结合后，整联蛋白受体定位于局部接触位点。这种活性是潜伏的，因为未被占据的整合素受体不定位于病灶接触。缺失分析表明，α胞质结构域是维持整合素受体潜伏期所必需的。我们目前对整合素后配体结合事件机制的假设是α和β胞质结构域的关系发生了变化，这克服了受体潜伏期。这种变化的一个可能机制涉及膜-细胞质界面的氨基酸残基。为了验证这一假设，我们在人整合素α（1）亚基中产生了点突变。这些突变对通过α（1）β（1）与其配体IV型胶原的粘附没有影响。然而，受体潜伏期在这些突变体之一中丢失，导致组成性局部接触定位。这种效果没有发生在受体与细胞内结构域的交换，这表明，损失的潜伏期的机制涉及的整合素链的相对运动。这些结果表明，在整合素受体中的后配体结合事件与α和β胞质结构域的位置变化相关的模型。
Localization of integrin receptors to focal contact sites occurs upon ligand binding. This activity is latent, since unoccupied integrin receptors do not localize to focal contacts. Deletion analysis has revealed that the alpha cytoplasmic domain is required for the maintenance of integrin receptor latency. Our current hypothesis for the mechanism of integrin post-ligand binding events is that there is a change in relationship of alpha and beta cytoplasmic domains, which overcomes receptor latency. One possible mechanism for such a change would involve the amino acid residues at the membrane-cytoplasm interface. To test this hypothesis, we have produced point mutations in the human integrin alpha(1) subunit. These mutations had no effect on the adhesion via alpha(1) beta(1) to its ligand, collagen IV. However, receptor latency is lost in one of these mutants, leading to constitutive focal contact localization. This effect did not occur in receptors with an exchange of intracellular domains, suggesting that the mechanism of loss of latency involves a relative motion of the integrin chains. These results suggest a model in which post-ligand binding events in integrin receptors are associated with changes in the position of the alpha and beta cytoplasmic domains.