Cholesterol exerts different modulatory effects at the cell surface of muscle and neuronal nicotinic acetylcholine receptors

BORRONI M.V; KAMEERBECK C.B; PEDICONI M.F.; BARRANTES F.J.

Ciudad Autónoma de Buenos Aires

Conferencia; 5th Special Conference of the International Society for Neurochemistry; 2012

Laboratorio de Neurobiología, UCA-Conicet

Cholesterol exerts a different modulation of surface muscle and neuronal acetylcholine nicotinic receptors Borroni V.a, Kameerbeck C.B.a , Pediconi M.F. a and Barrantes F.J.b a Instituto de Investigaciones Bioquímicas de Bahía Blanca, Consejo de Investigaciones Científicas y Técnicas (CONICET) /Universidad Nacional del Sur, 8000 Bahía Blanca, and b Laboratory of Molecular Neurobiology, Institute of Biomedical Res., UCA, and CONICET, 1107 Buenos Aires, Argentina. Communication at synapses requires the location and maintenance of receptors at specific sites. Factors controlling the distribution of receptors are critical determinants of the cell response to external signals. The nicotinic acetylcholine receptor (AChR) is the best characterized ligand-gated ion channel, found at neuromuscular junctions and central nervous system synapses. We have found that cholesterol (Chol), contributes to the homeostasis of muscle-type receptor levels at the plasmalemma (Kumari et al., J. Cell Biol., 2008; Borroni and Barrantes, J. Biol. Chem., 2011). Cyclodextrin-mediated acute Chol depletion lowered the number of cell-surface muscle AChRs in CHO-K1/A5 cells and C2C12 muscle cells. In contrast, the same treatment performed on cultured hippocampal neurons, increased the amount of α7 AChR at the plasmalemma. In addition, chronic Chol reduction mediated by Mevinolin, an inhibitor of Chol biosynthesis, augmented the cell-surface levels of α7 AChR and α4β2 neuronal AChR subtypes measured by fluorescence microscopy and radioactive ligand binding assays. The results suggest that Chol modulates surface AChR levels differentially in peripheral and central cholinergic synapses. Keywords: Nicotinic Acetylcholine Receptor; Cholesterol; hippocampal neurons