Subcellular localization and putative role of VPS13A/chorein in dopaminergic neuronal cells
Autor: | Masayuki Nakamura, Akira Sano, Mikio Iijima, Shosei Kishida, Yoshiaki Nishizawa, Takehiro Hayashi, Chihaya Koriyama, Michiko Kishida |
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Rok vydání: | 2012 |
Předmět: |
Neurite
Vesicular Transport Proteins Biophysics Nerve Tissue Proteins Biology PC12 Cells Biochemistry Exocytosis Mice Dopamine Cell Line Tumor medicine Animals Humans Molecular Biology Loss function Vacuolar protein sorting Dopaminergic Neurons Secretory Vesicles Synaptotagmin I Dopaminergic Cell Biology Subcellular localization Molecular biology Rats Neuroacanthocytosis medicine.drug |
Zdroj: | Biochemical and Biophysical Research Communications. 419:511-516 |
ISSN: | 0006-291X |
DOI: | 10.1016/j.bbrc.2012.02.047 |
Popis: | 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. |
Databáze: | OpenAIRE |
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