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Cytoplasmic Transport Signal is Involved in Phogrin Targeting and Localization to Secretory Granules
Author(s) -
Torii Seiji,
Saito Naoya,
Kawano Ayumi,
Zhao Shengli,
Izumi Tetsuro,
Takeuchi Toshiyuki
Publication year - 2005
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.1600-0854.2005.00353.x
Subject(s) - microbiology and biotechnology , biology , secretory protein , secretory pathway , golgi apparatus , signal peptide , secretory vesicle , endocytosis , protein targeting , transmembrane protein , cytoplasm , clathrin , signal transducing adaptor protein , endoplasmic reticulum , membrane protein , secretion , signal transduction , exocytosis , biochemistry , peptide sequence , cell , receptor , membrane , gene
Phogrin is an integral glycoprotein primarily expressed in neuroendocrine cells. The predominant localization of phogrin is on dense‐core secretory granules, and the lumenal domain has been shown to be involved in its efficient sorting to the regulated secretory pathway. Here, we present data showing that a leucine‐based sorting signal [EExxxIL] within the cytoplasmic tail contributes its steady‐state localization to secretory granules. Deletion mutants in the tail region failed to represent granular distribution in pancreatic β‐cell line, MIN6, and anterior pituitary cell line, AtT‐20. A sorting signal mutant with two glutamic acids substituted into alanines (EE/AA) is primarily accumulated in the Golgi area instead of secretory granules, and another mutant (IL/AA) is trapped at the plasma membrane due to a defect in endocytosis. We further demonstrate that the leucine‐based sorting signal of phogrin specifically interacts with both adaptor protein (AP)‐1 and AP‐2 clathrin adaptor complexes in vitro . These observations, along with previous studies, suggest that distinct domains of phogrin mediate proper localization of this transmembrane protein on secretory granules.