title: Diacylglycerol levels modulate the cellular distribution of the nicotinic acetylcholine receptor.
abstract: 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 (30min-4h) whereas at longer times (18h) the AChR was shifted to intracellular compartments. Similarly, in cultured hippocampal neurons surface AChR levels increased as a result of DOG incubation for 4h. 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.
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca, Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina.
authors.forename: Constanza B
authors.initials: CB
authors.lastname: Kamerbeek
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca, Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina.
authors.forename: Melina V
authors.initials: MV
authors.lastname: Mateos
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca, Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina.
authors.forename: Ana S
authors.initials: AS
authors.lastname: Vallés
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca, Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Pediconi
authors.affiliation: Laboratory of Molecular Neurobiology, Institute for Biomedical Research UCA-CONICET, Faculty of Medical Sciences, Av. Alicia Moreau de Justo 1600, C1107AFF Buenos Aires, Argentina.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Barrantes
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca, Camino La Carrindanga km 7, 8000 Bahía Blanca, Argentina. Electronic address: vborroni@criba.edu.ar.
authors.forename: Virginia
authors.initials: V
authors.lastname: Borroni
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004075:Diglycerides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: C011439:1,2-diacylglycerol; D004075:Diglycerides; D004791:Enzyme Inhibitors; D011978:Receptors, Nicotinic; D011493:Protein Kinase C
keywords: Acetylcholine receptor; Diacylglycerol; Protein kinase C; Protein kinase D