Premium
Intracellular trafficking and secretion of cerebral dopamine neurotrophic factor in neurosecretory cells
Author(s) -
Sun ZongPeng,
Gong Lei,
Huang ShuHong,
Geng Zhao,
Cheng Lei,
Chen ZheYu
Publication year - 2011
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 - 10.1111/j.1471-4159.2011.07179.x
Subject(s) - secretion , dopaminergic , biology , microbiology and biotechnology , neurotrophic factors , endoplasmic reticulum , dopamine , neuroscience , endocrinology , biochemistry , receptor
J. Neurochem. (2011) 117 , 121–132. Abstract Cerebral dopamine neurotrophic factor (CDNF) is a novel evolutionary conserved protein which can protect and restore the function of dopaminergic neurons in the rat model of Parkinson’s disease, suggesting that CDNF might be beneficial for the treatment of Parkinson’s disease. CDNF is widely expressed in neurons in several brain regions including cerebral cortex, hippocampus, substantia nigra, striatum and cerebellum. Human CDNF is glycosylated and secreted from transiently transfected cells; however, the mechanism underlying CDNF secretion is currently unclear. In this study, we found that CDNF could be secreted primarily via the regulated secretion pathway in PC12 cells. The glycosylation of CDNF is not required for its secretion. Moreover, we identified two key subdomains in CDNF which are important for its intracellular localization and secretion. Disrupting helix‐1 of CDNF significantly reduces its constitutive and regulated secretion and the helix‐1 mutant is retained in the endoplasmic reticulum. Although helix‐7 mutation only decreases CDNF regulated secretion and has no effect on its constitutive secretion, which is further supported by the reduction in co‐localization of helix‐7 mutant with secretory granules. In all, these findings will advance our understanding of the molecular mechanism of CDNF trafficking and secretion.