Acetylcholinesterases of Rhipicephalus (Boophilus) microplus – Multiple gene expression presents an opportune model system for elucidation of multiple functions of AChEs

Acetylcholinesterase (AChE) is a key neural enzyme of both vertebrates and invertebrates, and is the biochemical target of organophosphate and carbamate pesticides for invertebrates, as well as vertebrate nerve agents, e.g., soman, tabun, VX, and others. AChE inhibitors are also key drugs among those approved by the FDA for management of Alzheimer’s disease. Vertebrates contain a single type of AChE gene producing multiple forms of AChE by alternative gene splicing and formation of multimeric protein complexes. AChE hydrolyzes the neurotransmitter, acetylcholine, but may play many other important roles in physiology and development. The remarkable complexity of AChE and its key role in neural transmission have presented significant difficulties for vertebrate studies of non-catalytic functions of AChE, although studies have implicated AChE in neuritogenesis, retina development, cell adhesion, synaptogenesis, amyloid fiber assembly, haematopoiesis, regulation of stress-induced responses, stem cell growth and differentiation, formation of basal lamina, and other non-classical functions. Some invertebrates contain multiple genes encoding AChE, e.g., nematodes (4), ticks (3), mosquitoes (2). Structural comparison of invertebrate AChEs with those of vertebrates may allow choice of AChE model systems with significantly reduced complexity and advantages for manipulation and experimentation in whole organisms that are implausible with many vertebrate systems. Use of appropriate model systems should provide opportunity for rapid advances in elucidation of non-classical functions of AChE that are conserved between vertebrate and invertebrate systems.