Morphoregulation by acetylcholinesterase in fibroblasts and astrocytes

Anderson, Alexandra; Ushakov, Dmitry S.; Ferenczi, Michael A.; Mori, Ryoichi; Martin, Paul; Saffell, Jane L.

doi:10.1002/jcp.21288

Cited by 43 publications

(31 citation statements)

References 73 publications

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“…AChE becomes localized to the apical surface by NF 46 (Fig. 1I-I″), consistent with a potential function in cell polarity (Anderson et al, 2008).…”

Section: Results and Discussion Ache Is Required For Gut Morphogenesissupporting

confidence: 49%

“…As FN is distributed in a radially polarized manner within the gut tube, AChE-FN interactions are likely to facilitate endoderm cell polarization, orienting the radial rearrangements that are crucial to drive intestinal elongation. Moreover, the broad expression of AChE and FN during metazoan development, wound healing and regeneration (Anderson et al, 2008;Bertrand et al, 2001;Bicker et al, 2004;de Almeida et al, 2016;Drews, 1975;Ohta et al, 2009) suggests that AChE could regulate a wide variety of morphogenetic events across numerous species.…”

Section: Discussionmentioning

confidence: 99%

“…dependent adhesion on LM (Anderson et al, 2008;Sharma et al, 2001), suggesting this interaction is cell type-specific. However, we did find that AChE MO-injected endoderm cells were significantly less adherent on FN compared with control MO-injected cells (Fig.…”

Section: Ache Is Required For Endoderm Adhesion To Fibronectinmentioning

confidence: 99%

“…Although AChE can influence rates of cell proliferation and apoptosis in other contexts (Anderson et al, 2008;Grisaru et al, 1999;Yang et al, 2002), these parameters are unaffected in AChE MO-injected guts (data not shown), suggesting that AChE regulates gut morphogenesis without affecting cell number. During the formation of the Xenopus intestine, endoderm cells radially intercalate, driving gut tube elongation as concentric cell layers are reduced from four or five cells thick to a single layer (Chalmers and Slack, 2000;Reed et al, 2009).…”

Section: Ache Is Required For Endoderm Rearrangement and Epithelializmentioning

confidence: 99%

“…This esterase activity is the target of widely used pesticides and pharmaceuticals (Mileson et al, 1998;Pope et al, 2005), yet the broad expression of AChE outside of the nervous system (Anderson et al, 2008;Bertrand et al, 2001;Bicker et al, 2004;Drews, 1975) and similarity to adhesion molecules (Botti et al, 1998;Darboux et al, 1996) suggest that it has additional functions. Indeed, in neuronal and non-neuronal cell lines, AChE promotes cell-substrate adhesion (Inkson et al, 2004;Johnson and Moore, 1999;Sharma et al, 2001;Syed et al, 2008), polarized cell migration (Anderson et al, 2008), cytoskeletal organization (Dupree and Bigbee, 1994;Keller et al, 2001) and cell differentiation (Grisaru et al, 1999;Xiang et al, 2008), independently of its esterase activity (Layer et al, 1993). However, the in vivo relevance of this putative multi-functionality is poorly substantiated, especially in non-neuronal contexts (Vogel-Hopker et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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

2017

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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.

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“…AChE becomes localized to the apical surface by NF 46 (Fig. 1I-I″), consistent with a potential function in cell polarity (Anderson et al, 2008).…”

Section: Results and Discussion Ache Is Required For Gut Morphogenesissupporting

confidence: 49%

Section: Discussionmentioning

confidence: 99%

Section: Ache Is Required For Endoderm Adhesion To Fibronectinmentioning

confidence: 99%

Section: Ache Is Required For Endoderm Rearrangement and Epithelializmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

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

2017

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Cholinesterasen mit Nebenjobs

Sperling¹,

Janine²,

Willbold³

et al. 2020

Biologie in unserer Zeit

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Zusammenfassung Sowohl die frühe phylogenetische und ontogenetische Existenz von cholinergen Systemen, als auch das Vorkommen in nicht‐neuronalen Geweben legen cholinerge und nicht‐cholinerge Funktionalitäten nahe, die weit über deren klassische Funktion an Synapsen hinausgehen. Die Fähigkeit von Cholinesterasen zur Bildung riesiger Proteinkomplexe eröffneten ihnen vielseitige Funktionsfelder. Schon in Stammzellen vertreten, begünstigen Cholinesterasen im Verbund mit Komponenten der Zellmatrix die Zelldifferenzierung; dabei erscheint ihre Enzymaktivität (teilweise) als nicht notwendig. Dies wurde durch Effekte inaktiver AChE in nicht‐neuronalen Zellen einerseits, und davon unabhängig durch die Entdeckung der CLAM‐Proteinfamilie beeindruckend untermauert. Vieles spricht somit dafür, dass die ursprünglichen Funktionsfelder der Cholinesterasen, wie auch von cholinergen Systemen insgesamt, in allgemeinen Zell‐Zell‐Wechselwirkungen zu suchen sind. Diese Einsichten wurden hier an einigen Zellkulturstudien und ausgewählten Beispielen der Normalentwicklung dargestellt. In der Wirbeltierretina beeinflussen die als erste differenzierenden cholinergen Amakrinzellen die Netzwerkbildung. Nicht weniger bedeutend ist das cholinerge System bei der Bildung von Röhrenknochen. Acetylcholin beschleunigt die Knochenbildung, und die Cholinesterasen regulieren dabei nicht nur dessen Konzentration, sondern spielen beide zudem strukturelle Rollen. Ebenso überzeugend ist eine Studie an Froschlarven, die zeigt, dass bei der Darmbildung von Xenopus laevis sehr wohl das AChE‐Protein, aber nicht dessen Enzymaktivität beteiligt ist. Die volle Aufklärung der Wirkungsweise der Cholinesterasen ist notwendig, denn eine Vielzahl von spezifischen Anticholinesterasen finden breite Anwendungen in wichtigen gesellschaftlichen Bereichen (Landwirtschaft, Gesundheit, Sicherheit). Die Forschung hat dies erkannt und widmet sich verstärkt nicht nur den Cholinesterasen, sondern insgesamt der Aufklärung nicht‐neuronaler cholinerger Systeme (NNCS).

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Acetylcholinesterase

Pérez-Aguilar

Vidal

Gómez-Olivares

et al. 2016

Encyclopedia of Signaling Molecules

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Acetylcholine-hydrolase; AChE Historical background Since its discovery in 1914, acetylcholinesterase (AChE) has attracted attention of many research groups, making AChE one of the most studied proteins. The great physiological relevance of AChE has prompted exhaustive research to know its substrate preference, catalytic mechanism, sensitivity to inhibitors, active site topology, entrance and exiting of substrates, inhibitors and products, and other aspects of AChE-related

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Morphoregulation by acetylcholinesterase in fibroblasts and astrocytes

Cited by 43 publications

References 73 publications

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

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

Cholinesterasen mit Nebenjobs

Acetylcholinesterase

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