SYNAPTIC AND EPIDERMAL ACCUMULATIONS OF HUMAN ACETYLCHOLINESTERASE ARE ENCODED BY ALTERNATIVE 3'-TERMINAL EXONS

Tissue-specific heterogeneity among mammalian acetylcholinesterases (A ChE) has been associated with 3' alternative splicing of the primary A ChE gene transcript, We have previously demonstrated that human AChE D NA encoding the brain and muscle AChE form and bearing the 3' exon E6 (ACHE-E6) induces accumulation of catalytically active AChE in myotome s and neuromuscular junctions (NMJs) of 2- and 3-day-old Xenopus embry os, Here, we explore the possibility that the 3'-terminal exons of two alternative human AChE cDNA constructs include evolutionarily conserv ed tissue-recognizable elements. To this end, DNAs encoding alternativ e human AChE mRNAs were microinjected into cleaving embryos of Xenopus laevis, In contrast to the myotomal expression demonstrated by ACHE E 6, DNA carrying intron I4 and alternative exon E5 (ACHE-I4/E5) promote d punctuated staining of epidermal cells and secretion of AChE into th e external medium, Moreover, ACHE-E6-injected embryos displayed enhanc ed NMJ development, whereas ACHE-I4/E5-derived enzyme was conspicuousl y absent from muscles and NMJs and its expression in embryos had no ap parent effect on NMJ development. In addition, cell-associated AChE fr om embryos injected with ACHE-I4/E5 DNA was biochemically distinct fro m that encoded by the muscle-expressible ACHE-E6, displaying higher el ectrophoretic mobility and greater solubility in low-salt buffer, Thes e findings suggest that alternative 3'-terminal exons dictate tissue-s pecific accumulation and a particular biological role(s) of AChE, asso ciate the 3' exon E6 with NMJ development, and indicate the existence of a putative secretory AChE form derived from the alternative I4/E5 A ChE mRNA.