Carboxypeptidase e cytoplasmic tail-driven vesicle transport is key for activity-dependent secretion of peptide hormones
Carboxypeptidase e cytoplasmic tail-driven vesicle transport is key for activity-dependent secretion of peptide hormones
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DOI：
10.1210/me.2007-0473
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发表时间：
2008-04-01
影响因子：
--
通讯作者：
Loh, Y. Peng
中科院分区：
文献类型：
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作者：
Park, Joshua J.;Cawley, Niamh X.;Loh, Y. Peng
肽类激素从细胞体到质膜的囊泡转运对于内分泌功能是重要的，但它是如何实现的尚不清楚。在这里，我们揭示了一种机制，其中发现在前阿黑皮素（POMC）/促肾上腺皮质激素囊泡的跨膜羧肽酶E（CPE）的细胞质尾巴与微管为基础的电机相互作用，以控制这些囊泡的运输到垂体细胞中的释放位点。在活细胞中CPE尾部的过表达显著降低了POMC/ACTH-和CPE-含有囊泡运动进入细胞过程的速度和距离。生物化学研究表明，CPE尾部与dynactin相互作用，而dynactin反过来又招募微管加端马达驱动蛋白2和驱动蛋白3。CPE尾的过表达抑制AtT 20细胞刺激的ACTH分泌。因此，CPE的胞质尾相互作用与dynactin驱动蛋白2/驱动蛋白3在POMC囊泡的活动依赖性分泌的运输中起着重要的作用。
Vesicular transport of peptide hormones from the cell body to the plasma membrane for activity-dependent secretion is important for endocrine function, but how it is achieved is unclear. Here we uncover a mechanism in which the cytoplasmic tail of transmembrane carboxypeptidase E (CPE) found in proopiomelanocotin (POMC)/ACTH vesicles interacts with microtubule-based motors to control transport of these vesicles to the release site in pituitary cells. Overexpression of the CPE tail in live cells significantly reduced the velocity and distance of POMC/ACTH- and CPE-containing vesicle movement into the cell processes. Biochemical studies showed that the CPE tail interacted with dynactin, which, in turn, recruited microtubule plus-end motors kinesin 2 and kinesin 3. Overexpression of the CPE tail inhibited the stimulated secretion of ACTH from AtT20 cells. Thus, the CPE cytoplasmic tail interaction with dynactin-kinesin 2/kinesin 3 plays an important role in the transport of POMC vesicles for activity-dependent secretion.