The Adhesion Function on Acetylcholinesterase Is Located at the Peripheral Anionic Site

Johnson, Glynis; Moore, Samuel W.

doi:10.1006/bbrc.1999.0705

Cited by 85 publications

(52 citation statements)

References 25 publications

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“…These examples seem to indicate that the expression of AChE is not essential for cultured cells. On the other hand, AChE is known to promote cell proliferation in vertebrate and nematode cell lines (Huby et al, 1999;Ruben et al, 2004) and to play a role in cell adhesion (Johnson and Moore, 1999). In the NIH-SaPe-4 cell line, inhibition of AChE activity by eserine did not affect cell growth (Ohbayashi et al, 1997), eserine which inhibited 80-90% of AChE activity in NIAS-AeAl-2 cultured cells brought no effect and the recovery of the activity occurred in 5 d (Mizuno, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…If AChE has functions besides ACh hydrolysis (non-cholinergic function) in these cultured insect cells, AChE protein without catalytic activity must have a role. The 'peripheral' anionic site has been shown to be associated with the non-cholinergic functions of AChE (Johnson and Moore, 1999;Silman and Sussman, 2005). To elucidate the functions of AChE, gene-silencing experiments with RNA interference, for example, seem to be the best procedure for cultured cells.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, a question as to the functions of AChE except for the primary function mentioned above, arises because of the existence of two types of the enzyme in insects. Some functions of AChE such as cell growth, cell-substrate adhesion and neurite growth have been suggested in vertebrates (Layer et al, 1993;Huby et al, 1999;Johnson and Moore, 1999;Ruben et al, 2004;Silman and Sussman, 2005). On the other hand, several insect cell lines having AChE activity have been reported (Ohbayashi et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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cDNA identification and gene expression of two types of acetylcholinesterases in a cultured cell line of Aedes albopictus, compared to mosquito whole body extracts

Mizuno

Tomita

Kasai

et al. 2006

Appl. Entomol. Zool.

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Two cDNA sequences containing open reading frames encoding two types of acetylcholinesterase (AChE) precursors, Ace-orthologous AChE (AO-AChE) and Ace-paralogous AChE (AP-AChE), with 635 residues and 702 residues, respectively, were determined in Aedes albopictus by PCR-based techniques. The partial and whole cDNAs for AOAChE and AP-AChE, respectively, were also sequenced from a cultured cell line of mosquito, NIAS-AeAl-2, derived from Ae. albopictus neonatal larvae. Comparing the sequences of the respective AChEs between cultured cells and mosquito whole body extracts, many nucleotide polymorphisms were found in both AChE cDNAs but only one amino acid substitution. The expression level of AChE genes in the cultured cells was low, 1/2 and 1/7 that of the mosquito body for AO-AChE and AP-AChE, respectively. The expression ratio of AO-AChE/AP-AChE was 1/2 in the cultured cells. AP-AChE genes was more highly expressed than AO-AChE genes in both cultured cells and the mosquito body. In an enzyme assay, the activity of AChE per protein in the cultured cells was 1/8 that of the mosquito body. The function of AChE in cultured cells is discussed based on the present and previous papers.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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cDNA identification and gene expression of two types of acetylcholinesterases in a cultured cell line of Aedes albopictus, compared to mosquito whole body extracts

Mizuno

Tomita

Kasai

et al. 2006

Appl. Entomol. Zool.

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“…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%

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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“…Overstimulation of these receptors may lead to respiratory failure and death. AChE has been proposed to have a second function independent of its catalytic activity [1][2][3][4]9,11,[13][14][15][16]23,25,26,28,[30][31][32], possibly serving as a cell adhesion factor in morphogenesis…”

Section: Introductionmentioning

confidence: 99%

Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides

Lockridge¹

2002

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, Paperwork Reduction Project (0704-0188), Washington, DC 20503 AGENCY USE ONLY (Leave blank)2. REPORT DATE August 2 0 02 REPORT TYPE AND DATES COVEREDAnnual (1 Aug 01 -31 Jul 02) TITLE AND SUBTITLE Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides AUTHOR(S)Oksana Lockridge, Ph.D. FUNDING NUMBERS DAMD17-01-1-0776 PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES)University of Nebraska Medical Center Omaha, Nebraska 68198-6810 E-Mail: olockrid@unmc.edu Though acetylcholinesterase is the primary target of organophosphorus toxicants, our finding that acetylcholinesterase knockout mice are supersensitive to the lethal effects of VX, DFP, chlorpyrifos oxon, and iso-OMPA demonstrates that other important targets exist. The goal of this work is to identify non-acetylcholinesterase targets of organophosphorus toxicants. PERFORMING ORGANIZATION REPORT NUMBER SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES)UBiotinylated-organophosphate was used to label proteins in mouse brain.The labeled proteins were separated by polyacrylamide gel electrophoresis and visualized with avidin conjugated to a fluorophore.This method has yielded 29 organophosphorus-reactive protein bands in mouse brain.They range in size from 15 to 100 kDa.Rate constants for reaction with biotinylated organophosphate were measured for the 29 proteins as well as for purified human acetylcholinesterase and human butyrylcholinesterase.A method has been developed to screen proteins for reactivity with organophosphorus agents.This work is expected to identify new biological markers for low dose exposure to organophosphorus toxicants and to explain the neurologic symptoms of some of our Gulf War veterans. Introduction. The purpose of this work is to identify proteins that react with low doses of organophosphorus agents (OP). There is overwhelming evidence that acute toxicity of OP is due to inhibition of AChE. However, we have found that the AChE knockout mouse, which has zero AChE, is supersensitive to low doses of OP. The AChE -/-mouse dies at doses of OP that are not lethal to wild-type mice (Duysen et al., 2001;Duysen et al., 2002). This demonstrates that non-AChE targets are involved in OP toxicity. Our goal is to identify new biological markers of exposure to organophosphorus agents. Our strategy uses biotinylated OP to label proteins, which are then visualized with avidin conjugated to a fluorophore....

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The Adhesion Function on Acetylcholinesterase Is Located at the Peripheral Anionic Site

Cited by 85 publications

References 25 publications

cDNA identification and gene expression of two types of acetylcholinesterases in a cultured cell line of Aedes albopictus, compared to mosquito whole body extracts

cDNA identification and gene expression of two types of acetylcholinesterases in a cultured cell line of Aedes albopictus, compared to mosquito whole body extracts

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

Biochemical Markers for Exposure to Low Doses of Organophosphorus Insecticides

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