Molecular Mechanisms Controlling the Synapse-Specific Expression and Activity-Linked Regulation of Acetylcholinesterase in Skeletal Muscle Fibers

Abstract

Acetylcholinesterase (AChE) is mostly known for its pivotal role in the inactivation of acetylcholine at cholinergic synapses in both central and peripheral nervous systems. This enzyme displays a rich polymorphism since it exists as a variety of molecular forms that may be classified as either homomeric or heteromeric on the basis of their association with specialized structural subunits. Homomeric forms include the G, monomer and G₂ di-mer as well as a glycophospholipid-linked (GPI) dimer. Conversely, heteromers consist of: i) the asymmetric forms A₄, A₈ or A₁₂ in which 1, 2 or 3 soluble G₄ tetramers attach to a collagenic structural subunit, respectively; and ii) amphiphilic tetramers G₄ linked to a 20 kDa hydrophobic anchor. Although the functional significance of this polymorphism is still elusive, it has been suggested that it allows the placement of catalytically active subunits in distinct cell types and subcellular locations where each form can assume site-specific functions. In mammals for example, the asymmetric forms of AChE are exclusively expressed in differentiated muscle and neuronal cells whereas GPI-linked dimers are found preferentially in tissues of hematopoietic origin. Such varied patterns of expression suggest that expression of AChE involves several levels of regulatory mechanisms ranging from tissue-specific transcriptional control to highly regulated post-translational events.