Depletion of carboxypeptidase E, a regulated secretory pathway sorting receptor, causes misrouting and constitutive secretion of proinsulin and proenkephalin, but not chromogranin A.

作者: Emmanuel Normant , Y. Peng Loh

DOI: 10.1210/ENDO.139.4.5951

关键词:

摘要: Previous studies have shown that the prohormone POMC is sorted to regulated secretory pathway (RSP), at trans-Golgi network, by binding of a conformation-dependent sorting signal receptor, identified as membrane-bound carboxypeptidase E (CPE) (Cool et al., 1997, Cell, 88:73–83). In this study, role CPE receptor for other RSP proteins contain signals (proinsulin, proenkephalin, and chromogranin A) was investigated in neuroendocrine cells (Neuro-2a) stably expressing antisense RNA. Whereas these were depleted greater than 85%, electron microscopy showed they dense core granules identical wild-type Neuro-2a cells, indicating not essential granulogenesis. Secretion immunocytochemical that, endogenous proenkephalin transfected proinsulin/insulin localized punctate released via RSP. However, CPE-depleted...

参考文章(37)
H H Gerdes, P Rosa, E Phillips, P A Baeuerle, R Frank, P Argos, W B Huttner, The primary structure of human secretogranin II, a widespread tyrosine-sulfated secretory granule protein that exhibits low pH- and calcium-induced aggregation. Journal of Biological Chemistry. ,vol. 264, pp. 12009- 12015 ,(1989) , 10.1016/S0021-9258(18)80167-3
L D Fricker, B Das, R H Angeletti, Identification of the pH-dependent membrane anchor of carboxypeptidase E (EC 3.4.17.10) Journal of Biological Chemistry. ,vol. 265, pp. 2476- 2482 ,(1990) , 10.1016/S0021-9258(19)39824-2
S L Sabol, C M Liang, S Dandekar, L S Kranzler, In vitro biosynthesis and processing of immunologically identified methionine-enkephalin precursor protein. Journal of Biological Chemistry. ,vol. 258, pp. 2697- 2704 ,(1983) , 10.1016/S0021-9258(18)32982-X
Yong Koo Kang, Seung Hyun Yoo, Identification of the secretory vesicle membrane binding region of chromogranin A. FEBS Letters. ,vol. 404, pp. 87- 90 ,(1997) , 10.1016/S0014-5793(97)00099-9
K. I. J. Shennan, K. Docherty, N. A. Taylor, Calcium- and pH-dependent aggregation and membrane association of the precursor of the prohormone convertase PC2. Journal of Biological Chemistry. ,vol. 269, pp. 18646- 18650 ,(1994) , 10.1016/S0021-9258(17)32358-X
John W. M. Creemers, Elena F. Usac, Nicholas A. Bright, Jan-Willem Van de Loo, Erik Jansen, Wim J. M. Van de Ven, John C. Hutton, Identification of a Transferable Sorting Domain for the Regulated Pathway in the Prohormone Convertase PC2 Journal of Biological Chemistry. ,vol. 271, pp. 25284- 25291 ,(1996) , 10.1074/JBC.271.41.25284
E Chanat, W B Huttner, Milieu-induced, selective aggregation of regulated secretory proteins in the trans-Golgi network. Journal of Cell Biology. ,vol. 115, pp. 1505- 1519 ,(1991) , 10.1083/JCB.115.6.1505