Synaptic and epidermal accumulations of human acetylcholinesterase are encoded by alternative 3'-terminal exons

S. Seidman, M. Sternfeld, R. B. Aziz-Aloya, R. Timberg, D. Kaufer-Nachum, H. Soreq*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Tissue-specific heterogeneity among mammalian acetylcholinesterases (ACHE) has been associated with 3' alternative splicing of the primary AChE gene transcript. We have previously demonstrated that human AChE DNA encoding the brain and muscle AChE form and bearing the 3' exon E6 (ACHE-E6) induces accumulation of catalytically active AChE in myotomes and neuromuscular junctions (NMJs) of 2- and 3-day-old Xenopus embryos. Here, we explore the possibility that the 3'-terminal exons of two alternative human AChE cDNA constructs include evolutionarily conserved tissue-recognizable elements. To this end, DNAs encoding alternative human AChE mRNAs were microinjected into cleaving embryos of Xenopus laevis. In contrast to the myotomal expression demonstrated by ACHE-E6, DNA carrying intron 14 and alternative exon E5 (ACHE-14/E5) promoted punctuated staining of epidermal cells and secretion of AChE into the external medium. Moreover, ACHE-E6-injected embryos displayed enhanced NMJ development, whereas ACHE-14/E5-derived enzyme was conspicuously absent from muscles and NMJs and its expression in embryos had no apparent effect on NMJ development. In addition, cell-associated AChE from embryos injected with ACHE-14/E5 DNA was biochemically distinct from that encoded by the muscle-expressible ACHE-E6, displaying higher electrophoretic mobility and greater solubility in low-salt buffer. These findings suggest that alternative 3'-terminal exons dictate tissue-specific accumulation and a particular biological role(s) of ACHE, associate the 3' exon E6 with NMJ development, and indicate the existence of a putative secretory AChE form derived from the alternative 14/E5 AChE mRNA.

Original languageEnglish
Pages (from-to)2993-3002
Number of pages10
JournalMolecular and Cellular Biology
Volume15
Issue number6
DOIs
StatePublished - 1995

Fingerprint

Dive into the research topics of 'Synaptic and epidermal accumulations of human acetylcholinesterase are encoded by alternative 3'-terminal exons'. Together they form a unique fingerprint.

Cite this