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

► Chorein was partially colocalized with Synaptotagmin I in PC12 cells. ► Chorein was localized to dense-core vesicle in mouse brain and PC12 cells. ► Expression of chorein C-terminus influenced dopamine release of PC12 cells. Chorea-acanthocytosis (ChAc) is a rare hereditary neurodegenerative disor...

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Published in:Biochemical and biophysical research communications 2012-03, Vol.419 (3), p.511-516
Main Authors: Hayashi, Takehiro, Kishida, Michiko, Nishizawa, Yoshiaki, Iijima, Mikio, Koriyama, Chihaya, Nakamura, Masayuki, Sano, Akira, Kishida, Shosei
Format: Article
Language:English
Subjects:
Animals
Cell Line, Tumor
Chorea-acanthocytosis
Chorein
Dense-core vesicle
Dopamine release
Dopaminergic Neurons - metabolism
Exocytosis
Humans
Mice
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neuroacanthocytosis - genetics
PC12 Cells
Rats
Secretory Vesicles - metabolism
Synaptotagmin I
Synaptotagmin I - metabolism
Vesicular Transport Proteins - genetics
Vesicular Transport Proteins - metabolism
VPS13A
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Summary:► Chorein was partially colocalized with Synaptotagmin I in PC12 cells. ► Chorein was localized to dense-core vesicle in mouse brain and PC12 cells. ► Expression of chorein C-terminus influenced dopamine release of PC12 cells. 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.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2012.02.047