engleski

A single mutation near the C-terminus in alfa/beta-fold protein family causes a defect in protein processing

An Arg to Cys mutation in the extracellular domain of neuroligin-3 (NL3) was recently found in a twin set with autism. The Cys substitution in NL3 causes altered intracellular protein trafficking, intracellular retention and diminished association with its cognate partner, beta-neurexin. NL3, butyrylcholinesterase (BuChE), and acetylcholinesterase (AChE), as members of the alfa/beta-hydrolase fold family of proteins, share over 30% of amino acid identity in their extracellular domains. In particular, Arg451 in NL3 is conserved in the alfa/beta-hydrolase fold family being homologous to Arg386 in BuChE and Arg395 in AChE. A Cys substitution at the homologous Arg in the BuChE was found studying post-succinylcholine apnea in an Australian population. We have made the homologous mutation in the mouse AChE and BuChE genes and showed that the Arg to Cys mutations resulted in identical alterations in the cellular phenotype for the various members of the alfa/beta-hydrolase fold family proteins.

cellular trafficking; cysteine mutation; acetylcholinesterase; autism; silent variant; butyrylcholinesterase

Rad je prošireni sažetak (Extended abstract)