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Dibasic cleavage site is required for sorting to the regulated secretory pathway for both pro‐ and neuropeptide Y
Author(s) -
Brakch Noureddine,
Allemandou Flore,
Cavadas Claudia,
Grouzmann Eric,
Brunner Hans R.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00919.x
Subject(s) - cycloheximide , secretion , protein kinase c , secretory protein , protein kinase a , secretory pathway , cleavage (geology) , dibasic acid , signal transduction , biochemistry , microbiology and biotechnology , neuropeptide y receptor , biology , chemistry , kinase , neuropeptide , protein biosynthesis , receptor , cell , golgi apparatus , paleontology , fracture (geology) , polymer chemistry
To investigate the signals governing routing of biologically active peptides to the regulated secretory pathway, we have expressed mutated and non‐mutated proneuropeptide Y (ProNPY) in pituitary‐derived AtT20 cells. The mutations were carried out on dibasic cleavage site and or ProNPY C‐terminal sequence. Targeting to the regulated secretory pathway was studied using protein kinase A (8‐BrcAMP), protein kinase C (phorbol myristate acetate) specific activators and protein synthesis inhibitor cycloheximide, and by pulse chase. The analysis of expressed peptides in cells and culture media indicated that: neuropeptide Y (NPY) and ProNPY were differently secreted, whilst NPY was exclusively secreted via regulatory pathway; ProNPY was secreted via regulated and constitutive‐like secretory pathways. ProNPY secretion behaviour was not Proteolytic cleavage efficiency‐dependent. The dibasic cleavage was essential for ProNPY and NPY cAMP‐dependent regulated secretion and may have function as a retention signal.