Assembly, stability and secretion of acetylcholinesterase in skeletal muscle fibres.

Abstract

The AChE gene encodes three mRNAs; R, H and T differing in their choice of C-terminal exons. Of these, AChET is exclusively accumulated in the synaptic compartment of adult skeletal muscle fibres. The mechanisms underlying the tissue-specific expression of the T forms as well the targeting of AChE to the neuromuscular junction have yet to be elucidated. To this end, we examined factors influencing the expression of AChE by transfection of C2C12 muscle cells and direct gene transfer in rodent hindlimb muscles. Transfection of C2C12 muscle cells with cDNAs encoding H and T resulted in high levels of enzyme activity. The H non-muscle subunit was preferentially expressed, several-fold more than the T subunit. Furthermore, transfection of myoblasts with a cDNA containing all the sequences necessary for expression of all AChE splice variants resulted only in expression of T subunits. This indicated that selective expression in muscle fibres is due to exclusive splicing of T mRNA from the primary transcript. (Abstract shortened by UMI.)