Quality control of a mutant plasma membrane ATPase: ubiquitylation prevents cell-surface stability
Quality control of a mutant plasma membrane ATPase: ubiquitylation prevents cell-surface stability
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DOI：
10.1242/jcs.02749
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发表时间：
2006-01-15
影响因子：
4
通讯作者：
Chang, A
中科院分区：
文献类型：
--
作者：
Liu, Y;Chang, A
质膜ATP酶Pma 1在细胞表面具有显著的寿命。与野生型蛋白质相反，温度敏感突变体Pma 1 -10是错误折叠的，并经历了从细胞表面的液泡降解的快速去除。在限制性温度下，Pma 1 -10在到达质膜之前或之后变得泛素化。Pma 1 -10的质膜内化和液泡降解依赖于epsin Ent 1的泛素相互作用基序（UIM），表明内吞机制对泛素化底物的识别。令人惊讶的是，泛素化的Pma 1 -10逆转时，其内化被阻断在end 3突变体。在这些条件下，Pma 1 -10获得与洗涤剂不溶性的糖脂富集复合物（DIG）的结合，这被认为促进野生型Pma 1的稳定性。泛素化不引起DIG排除，因为Pma 1-Ub融合蛋白不被显著地从DIG中排除。我们认为，泛素化的Pma 1 -10代表了一个组件的质量控制机制，目标是从质膜上去除错误折叠的蛋白质。Pma 1 -10的泛素化引起的快速内化可能会抢先建立稳定的相互作用。
The plasma membrane ATPase, Pma1, has remarkable longevity at the cell surface. In contrast to the wild-type protein, the temperature-sensitive mutant Pma1-10 is misfolded and undergoes rapid removal from the cell surface for vacuolar degradation. At the restrictive temperature, Pma1-10 becomes ubiquitylated before or upon arrival at the plasma membrane. Internalization from the plasma membrane and vacuolar degradation of Pma1-10 is dependent on the ubiquitin-interacting motif (UIM) of the epsin Ent1, suggesting recognition of ubiquitylated substrate by the endocytic machinery. Surprisingly, ubiquitylation of Pma1-10 is reversed when its internalization is blocked in an end3 mutant. Under these conditions, Pma1-10 acquires association with detergent-insoluble, glycolipid-enriched complexes (DIGs) which has been suggested to promote stability of wild-type Pma1. Ubiquitylation does not cause DIG exclusion because a Pma1-Ub fusion protein is not significantly excluded from DIGs. We suggest that ubiquitylation of Pma1-10 represents a component of a quality control mechanism that targets the misfolded protein for removal from the plasma membrane. Rapid internalization of Pma1-10 caused by its ubiquitylation may preempt establishment of stabilizing interactions.