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Publication : Subcellular localization and putative role of VPS13A/chorein in dopaminergic neuronal cells.

First Author  Hayashi T Year  2012
Journal  Biochem Biophys Res Commun Volume  419
Issue  3 Pages  511-6
PubMed ID  22366033 Mgi Jnum  J:182594
Mgi Id  MGI:5316152 Doi  10.1016/j.bbrc.2012.02.047
Citation  Hayashi T, et al. (2012) Subcellular localization and putative role of VPS13A/chorein in dopaminergic neuronal cells. Biochem Biophys Res Commun 419(3):511-6
abstractText  Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene encoding chorein. Although a deficiency in chorein function leads to apoptosis of striatal neurons in ChAc model mouse, its detailed subcellular localization and physiological role remain unclear. In this study, we produced two anti-chorein polyclonal antibodies and examined the intracellular localization of endogenous chorein in neuronal cells. Immunocytochemically, chorein was observed in the termini of extended neurites and partially colocalized with synaptotagmin I in differentiated PC12 cells. Subcellular localization analysis by sucrose density gradient fractionation showed that chorein and synaptotagmin I were located in dense-core vesicles (DCVs), which contain dopamine. In addition, PC12 cells stably expressing carboxyterminal fragment of chorein increased K(+)-induced dopamine release. Taken together, these results suggest that chorein is involved in exocytosis of DCV.
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