Biosynthesis of the Molecular Forms of Acetylcholinesterase

Vertebrates possess a variety of forms of acetylcholinesterase (AChE), as schematically illustrated in Figure 1. These forms present the same catalytic activity, but differ in their quaternary structure and in their interactions with membranes or with the extra-cellular matrix (basal lamina) (for reviews, see Massoulie and Bon, 1982; Massoulie and Toutant, 1988; Massoulie et al., in press). The catalytic subunits are generated from a single gene, they undergo various post-translational modifications and in some cases associate with structural subunits. Alternative splicing, together with the use of several transcription origins and polyadenylation signals, generate multiple mRNAs (Sikorav et al., 1987, 1988; Schumacher et al., 1988; Maulet et al., 1990). The coding sequence, however, seems to be modified only by alternative splicing of its 3' region. In Torpedo, the major part of this coding sequence, common to all mRNAs, is included in a large exon I (1678 nucleotides, from the initiation codon of T. marmorata AChE) and a small exon H (167 nucleotides) (Maulet et al., 1990). Exon II may be spliced to either exon IIIH or exon IIIT, generating the two kinds of catalytic subunits, H and T. These subunits constitute, respectively, the two main molecular forms occurring in the electric organ: the glycolipid (GPI)-anchored dimers and the collagen-tailed asymmetric forms. We do not designate the alternative exons and the corresponding catalytic subunits by the same letters as the globular (G) and asymmetric (A) molecular forms, because the distinction based on the general quaternary structure of the molecules does not coincide with the nature of their catalytic subunits: while collagen-tailed forms A forms contain only T subunits, different types of globular G forms may include either H or T subunits. In addition, a third type of catalytic subunit may be generated by an mRNA structure in which exon II is continued by the adjacent genomic sequence.