title: Cytoplasmic transport signal is involved in phogrin targeting and localization to secretory granules.
abstract: 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 beta-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.
authors.affiliation: Laboratory of Secretion Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Torii
authors.forename: Naoya
authors.initials: N
authors.lastname: Saito
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kawano
authors.forename: Shengli
authors.initials: S
authors.lastname: Zhao
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Izumi
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000818:Animals; D015704:CD4 Antigens / Q000235:genetics; D045744:Cell Line, Tumor; D006801:Humans; D007340:Insulinoma / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D022142:Secretory Vesicles / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D008565:Membrane Proteins; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; C102889:PTPRN2 protein, human; D017027:Protein Tyrosine Phosphatases; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8