Premium
Luminal Interaction of Phogrin with Carboxypeptidase E for Effective Targeting to Secretory Granules
Author(s) -
Saito Naoya,
Takeuchi Toshiyuki,
Kawano Ayumi,
Hosaka Masahiro,
Hou Ni,
Torii Seiji
Publication year - 2011
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2011.01159.x
Subject(s) - biology , microbiology and biotechnology , clathrin , carboxypeptidase , mutant , golgi apparatus , signal transducing adaptor protein , protein targeting , phosphotyrosine binding domain , receptor , protein tyrosine phosphatase , biochemistry , endocytosis , signal transduction , sh2 domain , endoplasmic reticulum , membrane protein , enzyme , gene , membrane
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.