Nicotinic acetylcholine receptor internalization via a novel endocytic pathway.

BORRONI V; KUMARI S; CHANDA B; MASSOL RH; CHAUDHRY A; MAYOR S; BARRANTES FJ

Rosario, Sta Fe

Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Endocytosis of the nicotinic acetylcholine receptor (AChR) is proposed to be a major mechanism of neuromodulation at neuromuscular junctions and in pathology of many diseases of cholinergic synapses in the central nervous system, but it is still poorly understood. We have characterized the endocytic mechanism of the AChR in CHO-K1/A5 cells, a Chinese hamster ovary (CHO) cell line heterologously expressing murine adult type receptor. Fluorescence derivatives of the competitive antagonist á-bungarotoxin (áBTX) were used to label the AChR in living cells. AChR was mostly distributed at the cell-surface; binding of áBTX shifted the distribution of the AChR to an internal pool coincident with Golgi and late endosomal markers. Internalization takes place via a clathrin- caveolin- and dynaminindependent pathway that depends on the integrity of the cytoskeletal network. The ligand-induced endocytic processes revealed here in a simple heterologous mammalian cell system may shed light on the dynamics of receptor internalization at the cholinergic synapse.