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

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• 作者：Takehiro Hayashi^a ; ^b ; ¹ ; Michiko Kishida^a ; ¹ ; Yoshiaki Nishizawa^c ; Mikio Iijima^a ; Chihaya Koriyama^d ; Masayuki Nakamura^b ; Akira Sano^b ; Shosei Kishida^a ; ^{shosei@m2.kufm.kagoshima-u.ac.jp}
• 关键词：Chorea-acanthocytosis ; VPS13A ; Chorein ; Synaptotagmin I ; Dense-core vesicle ; Dopamine release
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：16 March, 2012
• 卷：419
• 期：3
• 页码：511-516
• 文件大小：644 K

摘要

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.