Luminal interaction of phogrin with carboxypeptidase E for effective targeting to secretory granules.
Traffic
; 12(4): 499-506, 2011 Apr.
Article
en En
| MEDLINE
| ID: mdl-21210912
Phogrin, a receptor tyrosine phosphatase-like protein, is localized to dense-core secretory granules (SGs) in various neuroendocrine cells. A previous report showed that the N-terminal luminal domain mediates targeting of this protein to SGs in AtT-20 cells. Here, we show that the luminal domain specifically interacts with carboxypeptidase E (CPE), one of the key proteins involved in peptide hormone sorting, in a weakly acidic condition. The luminal domain consists of pro-sequence domain (pro) and subsequent N-side mature domain and the pro domain was preferentially required for phogrin interaction with CPE and for its targeting to SGs. Small interfering RNA-directed reduction of the CPE protein level resulted in an improper accumulation of phogrin at the trans-Golgi network in AtT-20 cells. This finding indicates that CPE is involved in the sorting process of phogrin to SGs. However, SG localization of CPE was hindered by overexpression of the phogrin mutants that lack the transport motif of binding to clathrin adaptor complexes. Phogrin-depleted AtT-20 cells also exhibited reduced CPE targeting and increased CPE degradation. Our results suggest that the luminal interaction between phogrin and CPE contributes to their targeting to SGs in a cooperative manner in neuroendocrine cells.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Vesículas Secretoras
/
Carboxipeptidasa H
/
Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores
/
Proteínas de la Membrana
Límite:
Animals
Idioma:
En
Revista:
Traffic
Asunto de la revista:
FISIOLOGIA
Año:
2011
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Reino Unido