Diacylglycerol levels modulate the cellular distribution of the nicotinic acetylcholine receptor

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• 作者：Constanza B. Kamerbeek^a ; Melina V. Mateos^a ; Ana S. Vallé ; s^a ; Marí ; a F. Pediconi^a ; Francisco J. Barrantes^b ; Virginia Borroni^a ; ^{vborroni@criba.edu.ar" class="auth_mail" title="E-mail the corresponding author} ; ^{mvirborroni@gmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：4α-PMA ; 4α-phorbol 12-myristate 13-acetate ; AChR ; muscle-type nicotinic acetylcholine receptor ; aPKC ; atypical protein kinase C ; BTX ; α-bungarotoxin ; cPKC ; classical protein kinase C ; CPT ; choline phosphotransferase ; DAG ; diacylglycerol ; DAGK ; diacylglycerol kinase ; DOG ; dioctanoylglycerol ; GGOH ; geranylgeraniol ; nPKC ; novel protein kinase C ; PC ; phosphatidylcholine ; PDBu ; phorbol 12-13-di butyrate ; PKD ; protein kinase D ; PVDF ; polyvinylidene fluoride ; ROT ; rottlerin ; TTBS ; Tween&ndash ; Tris buff
• 刊名：International Journal of Biochemistry and Cell Biology
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：74
• 期：Complete
• 页码：1-11
• 全文大小：2258 K

文摘

Diacylglycerol (DAG), a second messenger involved in different cell signaling cascades, activates protein kinase C (PKC) and D (PKD), among other kinases. The present work analyzes the effects resulting from the alteration of DAG levels on neuronal and muscle nicotinic acetylcholine receptor (AChR) distribution. We employ CHO-K1/A5 cells, expressing adult muscle-type AChR in a stable manner, and hippocampal neurons, which endogenously express various subtypes of neuronal AChR. CHO-K1/A5 cells treated with dioctanoylglycerol (DOG) for different periods showed augmented AChR cell surface levels at short incubation times (30 min–4 h) whereas at longer times (18 h) the AChR was shifted to intracellular compartments. Similarly, in cultured hippocampal neurons surface AChR levels increased as a result of DOG incubation for 4 h. Inhibition of endogenous DAG catabolism produced changes in AChR distribution similar to those induced by DOG treatment. Specific enzyme inhibitors and Western blot assays revealed that DAGs exert their effect on AChR distribution through the modulation of the activity of classical PKC (cPKC), novel PKC (nPKC) and PKD activity.