Regulated resurfacing of a somatostatin receptor storage compartment fine-tunes pituitary secretion
Regulated resurfacing of a somatostatin receptor storage compartment fine-tunes pituitary secretion
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DOI：
10.1083/jcb.201904054
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发表时间：
2020-01-06
影响因子：
7.8
通讯作者：
McPherson, Peter S.
中科院分区：
文献类型：
--
作者：
Alshafie, Walaa;Francis, Vincent;McPherson, Peter S.
由胰岛素受体激活驱动的葡萄糖转运蛋白GLUT 4的表面化提供了依赖于细胞内储存室的动员的稳态响应的原型实例。在这里，我们将这一概念推广到G蛋白偶联受体，生长抑素受体亚型2（SSTR 2），在垂体细胞。在促肾上腺皮质激素的内化后，SSTR 2移动到一个核外突触融合蛋白-6阳性的隔室，在那里它一直保持，直到促肾上腺皮质激素释放因子（CRF）刺激促肾上腺皮质激素，于是SSTR 2退出隔室突触融合蛋白-6阳性囊泡/管状载体，依赖于Rab 10与质膜融合。由于SSTR 2激活拮抗CRF介导的激素释放，这种储存/表面重塑机制可能允许生理稳态反馈系统。事实上，我们发现，SSTR 2移动从细胞内隔室的细胞表面在垂体生长激素，伴随着增加血清生长激素（GH）在自然生长激素周期。因此，我们的数据提供了一种机制，通过该机制，信号介导的质膜表面的SSTR 2可以微调垂体激素的释放。
The surfacing of the glucose transporter GLUT4 driven by insulin receptor activation provides the prototypic example of a homeostasis response dependent on mobilization of an intracellular storage compartment. Here, we generalize this concept to a G protein-coupled receptor, somatostatin receptor subtype 2 (SSTR2), in pituitary cells. Following internalization in corticotropes, SSTR2 moves to a juxtanuclear syntaxin-6-positive compartment, where it remains until the corticotropes are stimulated with corticotropin releasing factor (CRF), whereupon SSTR2 exits the compartment on syntaxin-6-positive vesicular/tubular carriers that depend on Rab10 for their fusion with the plasma membrane. As SSTR2 activation antagonizes CRF-mediated hormone release, this storage/resurfacing mechanism may allow for a physiological homeostatic feedback system. In fact, we find that SSTR2 moves from an intracellular compartment to the cell surface in pituitary gland somatotropes, concomitant with increasing levels of serum growth hormone (GH) during natural GH cycles. Our data thus provide a mechanism by which signaling-mediated plasma membrane resurfacing of SSTR2 can fine-tune pituitary hormone release.