Synaptic and Epidermal Accumulations of Human Acetylcholinesterase Are Encoded by Alternative 3′-Terminal Exons

Seidman, Shlomo; Sternfeld, M.; Aziz-Aloya, Revital Ben; Timberg, Rina; Kaufer-Nachum, Daniela; Soreq, Hermona

doi:10.1128/mcb.15.6.2993

Cited by 75 publications

(69 citation statements)

References 30 publications

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“…These proportions also depend on the nature and state of differentiation of the cell; for example, it varies during development of the nervous system (for review, see Ref. 1), and AChE T subunits are expressed in a tissue-specific manner in Xenopus embryos, even under the control of a viral promoter (29,30). In culture, the yield of AChE activity was markedly less in rat basoleukemia cells than in COS cells, in parallel transient transfections (17).…”

Section: Discussionmentioning

confidence: 99%

Quaternary Associations of Acetylcholinesterase

Bon

Massoulié

1997

Journal of Biological Chemistry

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We investigated the production of acetylcholinesterase of type T (AChE T ) in COS cells during transient transfection. When expressed alone, Torpedo AChE T remains essentially intracellular, forming dimers and tetramers; in contrast, rat AChE T is secreted and produces mostly amphiphilic monomers (G 1 a ) and dimers (G 2 a ), together with smaller proportions of nonamphiphilic (G 4 na ) tetramers, amphiphilic tetramers (G 4 a ), and an unstable higher polymer (13.7 S). The latter two forms have not been described before. We show that secreted G

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Section: Discussionmentioning

confidence: 99%

Quaternary Associations of Acetylcholinesterase

Bon

Massoulié

1997

Journal of Biological Chemistry

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“…Thus, we examined the initial response of AChE mRNA to SCG axotomy. Because the AChE T transcript is predominantly expressed in neurons, we focused on the level of expression of this mRNA (Legay et al, 1993;Seidman et al, 1995). As illustrated in Figure 3, AChE mRNA levels decreased dramatically to ϳ50% of sham-operated levels ( p Ͻ 0.0001) within 1 d of axotomy.…”

Section: Hud Binds Ache Transcripts In Vivomentioning

confidence: 99%

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

Deschênes‐Furry¹,

Mousavi²,

Bolognani³

et al. 2007

J. Neurosci.

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After axotomy, expression of acetylcholinesterase (AChE) is greatly reduced in the superior cervical ganglion (SCG); however, the molecular events involved in this response remain unknown. Here, we first examined AChE mRNA levels in the brain of transgenic mice that overexpress human HuD. Both in situ hybridization and reverse transcription-PCR demonstrated that AChE transcript levels were increased by more than twofold in the hippocampus of HuD transgenic mice. Additionally, direct interaction between the HuD transgene product and AChE mRNA was observed. Next, we examined the role of HuD in regulating AChE expression in intact and axotomized rat SCG neurons. After axotomy of the adult rat SCG neurons, AChE transcript levels decreased by 50 and 85% by the first and fourth day, respectively. In vitro mRNA decay assays indicated that the decrease in AChE mRNA levels resulted from changes in the stability of presynthesized transcripts. A combination of approaches performed using the region that directly encompasses an adenylate and uridylate (AU)-rich element within the AChE 3Ј-untranslated region demonstrated a decrease in RNA-protein complexes in response to axotomy of the SCG and, specifically, a decrease in HuD binding. After axotomy, HuD transcript and protein levels also decreased. Using a herpes simplex virus construct containing the human HuD sequence to infect SCG neurons in vivo, we found that AChE and GAP-43 mRNA levels were maintained in the SCG after axotomy. Together, the results of this study demonstrate that AChE expression in neurons of the rat SCG is regulated via post-transcriptional mechanisms that involve the AU-rich element and HuD.

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“…At the in vivo milieu, we reported a morphogenic activity for overexpressed human AChE in developing amphibian neuromuscular junctions (NMJs) (4,5). This activity was attributed primarily to modulations in synaptic acetylcholine levels and consequent changes in cholinergic neurotransmission.…”

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confidence: 99%

“…Fifty-micrometer-thick, paraformaldehyde͞glutaraldehyde-fixed spinal cord sections were stained for 30 min. Electron microscopy on 80-nm-thick sections and morphometric analyses were essentially as described (5). Student's t test was used to evaluate morphometric data.…”

mentioning

confidence: 99%

Acetylcholinesterase-transgenic mice display embryonic modulations in spinal cord choline acetyltransferase and neurexin Iβ gene expression followed by late-onset neuromotor deterioration

Andres

Beeri

Friedman

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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To explore the possibility that overproduction of neuronal acetylcholinesterase (AChE) confers changes in both cholinergic and morphogenic intercellular interactions, we studied developmental responses to neuronal AChE overexpression in motoneurons and neuromuscular junctions of AChE-transgenic mice. Perikarya of spinal cord motoneurons were consistently enlarged from embryonic through adult stages in AChE-transgenic mice. Atypical motoneuron development was accompanied by premature enhancement in the embryonic spinal cord expression of choline acetyltransferase mRNA, encoding the acetylcholine-synthesizing enzyme choline acetyltransferase. In contrast, the mRNA encoding for neurexin-I␤, the heterophilic ligand of the AChE-homologous neuronal cell surface protein neuroligin, was drastically lower in embryonic transgenic spinal cord than in controls. Postnatal cessation of these dual transcriptional responses was followed by late-onset deterioration in neuromotor performance that was associated with gross aberrations in neuromuscular ultrastructure and with pronounced amyotrophy. These findings demonstrate embryonic feedback mechanisms to neuronal AChE overexpression that are attributable to both cholinergic and cell-cell interaction pathways, suggesting that embryonic neurexin I␤ expression is concerted in vivo with AChE levels and indicating that postnatal changes in neuronal AChE-associated proteins may be involved in late-onset neuromotor pathologies.

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Synaptic and Epidermal Accumulations of Human Acetylcholinesterase Are Encoded by Alternative 3′-Terminal Exons

Cited by 75 publications

References 30 publications

Quaternary Associations of Acetylcholinesterase

Quaternary Associations of Acetylcholinesterase

The RNA-Binding Protein HuD Binds Acetylcholinesterase mRNA in Neurons and Regulates its Expression after Axotomy

Acetylcholinesterase-transgenic mice display embryonic modulations in spinal cord choline acetyltransferase and neurexin Iβ gene expression followed by late-onset neuromotor deterioration

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