Cool D R, Normant E, Shen F, Chen H C, Pannell L, Zhang Y, Loh Y P
Section on Cellular Neurobiology, Laboratory of Developmental Neurobiology, National Institute of Diabetes, Digestive, and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Cell. 1997 Jan 10;88(1):73-83. doi: 10.1016/s0092-8674(00)81860-7.
A proposed mechanism for sorting secretory proteins into granules for release via the regulated secretory pathway in endocrine-neuroendocrine cells involves binding the proteins to a sorting receptor at the trans-Golgi network, followed by budding and granule formation. We have identified such a sorting receptor as membrane-associated carboxypeptidase E (CPE) in pituitary Golgi-enriched and secretory granule membranes. CPE specifically bound regulated secretory pathway proteins, including prohormones, but not constitutively secreted proteins. We show that in the Cpe(fat) mutant mouse lacking CPE, the pituitary prohormone, pro-opiomelanocortin, was missorted to the constitutive pathway and secreted in an unregulated manner. Thus, obliteration of CPE, the sorting receptor, leads to multiple endocrine disorders in these genetically defective mice, including hyperproinsulinemia and infertility.
一种将分泌蛋白分选到颗粒中以便通过内分泌-神经内分泌细胞的调节性分泌途径释放的机制，涉及将蛋白质与反式高尔基体网络中的分选受体结合，随后出芽并形成颗粒。我们已确定这种分选受体是垂体富含高尔基体和分泌颗粒膜中的膜相关羧肽酶E（CPE）。CPE特异性结合包括激素原在内的调节性分泌途径蛋白，但不结合组成型分泌蛋白。我们发现，在缺乏CPE的Cpe（fat）突变小鼠中，垂体激素原阿黑皮素原被错误分选到组成型途径并以不受调节的方式分泌。因此，分选受体CPE的缺失导致这些基因缺陷小鼠出现多种内分泌紊乱，包括高胰岛素血症和不育。
