Acetylcholinesterase plays a non-neuronal, non-esterase role in organogenesis

Abstract

Acetylcholinesterase (AChE) is crucial for degrading acetylcholine at cholinergic synapses. In vitro studies suggest that, in addition to its role in nervous system signaling, AChE can also modulate nonneuronal cell properties, although it remains controversial whether AChE functions in this capacity in vivo. Here, we show that AChE plays an essential non-classical role in vertebrate gut morphogenesis. Exposure of Xenopus embryos to AChE-inhibiting chemicals results in severe defects in intestinal development. Tissuetargeted loss-of-function assays (via microinjection of antisense morpholino or CRISPR-Cas9) confirm that AChE is specifically required in the gut endoderm tissue, a non-neuronal cell population, where it mediates adhesion to fibronectin and regulates cell rearrangement events that drive gut lengthening and digestive epithelial morphogenesis. Notably, the classical esterase activity of AChE is dispensable for this activity. As AChE is deeply conserved, widely expressed outside of the nervous system, and the target of many environmental chemicals, these results have wide-reaching implications for development and toxicology.

Acetylcholine signaling system in progression of lung cancers

“…The substrate for AChE is ACh. The identification of ChEs in nonneuronal tissue, blood and body fluids indicates that these proteins have cellular functions which are independent of its ACh-hydrolytic activity (Jiang & Zhang, 2008;Pickett, Dush, & Nascone-Yoder, 2017;Pohanka, 2011;Soreq & Seidman, 2001;Xi, et al, 2015). HUVECs express enzymatically active AChE (Carvalho, Graca, Martins-Silva, & Saldanha, 2005).…”

Multi-organ characterisation of B-esterases in the European sea bass (Dicentrarchus labrax): Effects of the insecticide fipronil at two temperatures

“…An additional role for pseudocholinesterases that could gain importance under stressful conditions, or due to the presence of AChE inhibitors, would be to take over AChE tasks (Falugi and Aluigi, 2012). Moreover, the presence of AChE outside the nervous system indicates other roles for this enzyme in addition to its main implication in neural transmission (Soreq and Seidman, 2001;Pickett et al, 2017). Conversely, CEs are ubiquitously distributed in all phylogenetic groups, as well as among tissues/organs (Satoh and Hosokawa, 1998, J o u r n a l P r e -p r o o f 2006) where they may play roles yet to be unravelled.…”

Vangl2 coordinates cell rearrangements during gut elongation

“…For example, whereas CoMO‐injected endoderm cells exhibit levels of membrane‐localized beta‐catenin (a key component of adherens junctions) comparable to adjacent uninjected cells, Vangl2 MO‐injected cells display decreased or absent beta‐catenin (compare Figure F and K). Indeed, in an ex vivo cell dissociation/reaggregation assay designed to evaluate calcium‐dependent (ie, adherens junction‐mediated) intercellular adhesion (see Experimental Procedures), we detected significantly less reaggregation ( P < 0.05; Figure R) of cells derived from Vangl2 MO‐injected gut tubes than from CoMO‐injected guts (compare Figures N,O and P,Q), suggesting morphant cells have fewer and/or less stable adherens junctions. Despite their decreased adhesion, Vangl2‐deficient cells remain viable, as we do not detect apoptotic markers in the Vangl2 MO‐injected population (not shown).…”