Why so many forms of acetylcholinesterase?

Legay, Claire

doi:10.1002/(sici)1097-0029(20000401)49:1<56::aid-jemt7>3.0.co;2-r

Cited by 86 publications

(45 citation statements)

References 159 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The quail muscle cultures (QMCs) were fed with fresh medium on days three and five after plating, and on day three the medium was supplemented with 10 Ϫ6 M cytosine-arabinoside (Sigma) to inhibit fibroblast proliferation. Cultures were maintained in a 39°C in a watersaturated incubator with 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Limiting Role of Protein Disulfide Isomerase in the Expression of Collagen-tailed Acetylcholinesterase Forms in Muscle

Ruiz¹,

Rotundo

2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

The expression of acetylcholinesterase (AChE) in skeletal muscle is regulated by muscle activity; however, the underlying molecular mechanisms are incompletely understood. We show here that the expression of the synaptic collagen-tailed AChE form (ColQ-AChE) in quail muscle cultures can be regulated by muscle activity post-translationally. Inhibition of thiol oxidoreductase activity decreases expression of all active AChE forms. Likewise, primary quail myotubes transfected with protein disulfide isomerase (PDI) short hairpin RNAs showed a significant decrease of both the intracellular pool of all collagentailed AChE forms and cell surface AChE clusters. Conversely, overexpression of PDI, endoplasmic reticulum protein 72, or calnexin in muscle cells enhanced expression of all collagentailed AChE forms. Overexpression of PDI had the most dramatic effect with a 100% increase in the intracellular ColQAChE pool and cell surface enzyme activity. Moreover, the levels of PDI are regulated by muscle activity and correlate with the levels of ColQ-AChE and AChE tetramers. Finally, we demonstrate that PDI interacts directly with AChE intracellularly. These results show that collagen-tailed AChE form levels induced by muscle activity can be regulated by molecular chaperones and suggest that newly synthesized exportable proteins may compete for chaperone assistance during the folding process. Acetylcholinesterase (AChE)3 is an important component of the neuromuscular synapse where it rapidly terminates neurotransmission by hydrolyzing acetylcholine. Two separate genes encode the catalytic (AChE) and collagen tail (ColQ) subunits of the hetero-oligomeric collagen-tailed AChE forms expressed in skeletal muscle (for review, see Refs. 1-3). A single ColQAChE molecule consists of three catalytic AChE tetramers attached to a triple-helical collagen-like tail composed of three separate ColQ molecules. In some species and in some muscles, one (A4) or two (A8) tetramers of AChE attached to the triple helical ColQ subunits are observed. Each ColQ strand binds covalently to a tetramer of catalytic subunits, and each tetramer in turn consists of two dimers, with one dimer having its two C-terminal cysteine residues covalently linked to cysteine residues at the N terminus of ColQ. The other two catalytic subunits are also disulfide-linked to each other through the same residues (4, 5). Although many aspects of ColQ-AChE structure, function, and localization have been elucidated (for review, see Refs. 1-3), how this enzyme is regulated by muscle activity remains incompletely understood.Physiologically the expression of the synaptic ColQ-AChE form is regulated by the incoming nerve and by depolarization of the cell membrane (6 -11). Paradoxically, the direction of the regulation appears to be species-specific (for review, see Ref.3). In rats, for example, muscle paralysis due to denervation or induced pharmacologically leads to dramatic decrease in AChE transcripts and their accumulation at junctional sarcoplasm (12-14). Avian systems behav...

show abstract

Section: Methodsmentioning

confidence: 99%

“…Although many aspects of ColQ-AChE structure, function, and localization have been elucidated (for review, see Refs. [1][2][3], how this enzyme is regulated by muscle activity remains incompletely understood.…”

mentioning

confidence: 99%

Limiting Role of Protein Disulfide Isomerase in the Expression of Collagen-tailed Acetylcholinesterase Forms in Muscle

Ruiz¹,

Rotundo

2009

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Once released in the synaptic space, ACh level is largely controlled by acetylcholinesterase (AChE; EC 3.1.1.7) (Legay, 2000). The most abundant AChE form accumulated at the NMJ is the AChE T variant bound to a specific collagen, CollagenQ (ColQ) (Krejci et al, 1991(Krejci et al, , 1997.…”

Section: Introductionmentioning

confidence: 99%

ColQ Controls Postsynaptic Differentiation at the Neuromuscular Junction

Sigoillot¹,

Bourgeois²,

Lambergeon³

et al. 2010

J. Neurosci.

View full text Add to dashboard Cite

“…Acetylcholinesterase (AChE) is the enzyme responsible for terminating cholinergic neurotransmission in the CNS and peripheral nervous system (PNS), by rapid hydrolysis of acetylcholine (for review, see Massoulie et al, 1993;Legay, 2000;Soreq and Seidman, 2001;Rotundo, 2003). AChE is predominantly expressed in cholinergic tissues (muscle and neurons); however, it is also expressed in some noncholinergic neurons and nonexcitable cells, such as hematopoietic cells (Hammond et al, 1994;Bernard et al, 1995;Brimijoin and Hammond, 1996;Lev-Lehman et al, 1997;Chan et al, 1998).…”

Section: Introductionmentioning

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.

View full text Add to dashboard Cite

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.

show abstract

Why so many forms of acetylcholinesterase?

Cited by 86 publications

References 159 publications

Limiting Role of Protein Disulfide Isomerase in the Expression of Collagen-tailed Acetylcholinesterase Forms in Muscle

Limiting Role of Protein Disulfide Isomerase in the Expression of Collagen-tailed Acetylcholinesterase Forms in Muscle

ColQ Controls Postsynaptic Differentiation at the Neuromuscular Junction

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

Contact Info

Product

Resources

About