1. Chorein Sensitive Dopamine Release from Pheochromocytoma (PC12) Cells.
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Honisch, Sabina, Fehrenbacher, Birgit, Lebedeva, aleksandra, alesutan, Ioana, Castor, Tatsiana, alkahtani, Saad, alarifi, Saud, Schaller, Martin, Stournaras, Christos, and Lang, Florian
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PHEOCHROMOCYTOMA ,DOPAMINE regulation ,PHOSPHOINOSITIDES - Abstract
Background: Chorein, a protein supporting activation of phosphoinositide 3 kinase (PI3K), participates in the regulation of actin polymerization and cell survival. A loss of function mutation of the chorein encoding gene VPS13A (vacuolar protein sorting-associated protein 13A) leads to chorea-acanthocytosis (ChAc), a neurodegenerative disorder with simultaneous erythrocyte akanthocytosis. In blood platelets chorein deficiency has been shown to compromise expression of vesicle-associated membrane protein 8 (VAMP8) and thus degranulation. The present study explored whether chorein is similarly involved in VAMP8 expression and dopamine release of pheochromocytoma (PC12) cells. Methods: Chorein was down-regulated by silencing in PC12 cells. Transmission electron microscopy was employed to quantify the number of vesicles, RT-PCR to determine transcript levels, Western blotting to quantify protein expression and ELISA to determine dopamine release. Results: Chorein silencing significantly reduced the number of vesicles, VAMP8 transcript levels and VAMP8 protein abundance. Increase of extracellular K
+ from 5 mM to 40 mM resulted in marked stimulation of dopamine release, an effect significantly blunted by chorein silencing. Conclusions: Chorein deficiency down-regulates VAMP8 expression, vesicle numbers and dopamine release in pheochromocytoma cells. © 2015 The Author(s) Published by S. Karger AG, Basel [ABSTRACT FROM AUTHOR]- Published
- 2015
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