Ligand-dependent and -independent transforming growth factor-β receptor recycling regulated by clathrin-mediated endocytosis and Rab11
Ligand-dependent and -independent transforming growth factor-β receptor recycling regulated by clathrin-mediated endocytosis and Rab11
复制标题
DOI：
10.1091/mbc.e04-03-0245
复制
发表时间：
2004-09-01
影响因子：
3.3
通讯作者：
Leof, EB
中科院分区：
文献类型：
--
作者：
Mitchell, H;Choudhury, A;Leof, EB
转化生长因子-β (TGF-β) 家族中的蛋白质可识别跨膜丝氨酸/苏氨酸激酶，称为 I 型和 II 型受体。 TGF-β 与受体的结合导致受体下调和信号传导。虽然之前的工作主要集中在控制 TGF-β 信号传导的活动上，但最近的研究已经开始解决 TGF-β 受体的运输特性。在该报告中，表明受体在存在和不存在配体激活的情况下都会经历再循环，内化和再循环的速率不受配体结合的影响。当受体很可能通过网格蛋白包被的凹坑内化时，就会发生回收，然后通过依赖 rab11、不依赖 rab4 的机制返回质膜。总之，这些结果表明了一种机制，其中激活的 TGF-β 受体在一轮或多轮循环后定向至独特的内吞途径，进行下调和网格蛋白依赖性降解。
Proteins in the transforming growth factor-beta (TGF-beta) family recognize transmembrane serine/threonine kinases known as type I and type II receptors. Binding of TGF-beta to receptors results in receptor down-regulation and signaling. Whereas previous work has focused on activities controlling TGF-beta signaling, more recent studies have begun to address the trafficking properties of TGF-beta receptors. In this report, it is shown that receptors undergo recycling both in the presence and absence of ligand activation, with the rates of internalization and recycling being unaffected by ligand binding. Recycling occurs as receptors are most likely internalized through clathrin-coated pits, and then returned to the plasma membrane via a rab11-dependent, rab4-independent mechanism. Together, the results suggest a mechanism wherein activated TGF-beta receptors are directed to a distinct endocytic pathway for down-regulation and clathrin-dependent degradation after one or more rounds of recycling.