Distinct localization of collagen Q and PRiMA forms of acetylcholinesterase at the neuromuscular junction

Bernard, Véronique; Girard, Emmanuelle; Hrabovská, Anna; Camp, Shelley; Taylor, Palmer; Plaud, Benoît; Krejci, Éric

doi:10.1016/j.mcn.2010.09.010

Cited by 30 publications

(45 citation statements)

References 46 publications

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“…Skeletal muscle AChE does not seem to be involved, because AChE1irr KO mice, which lack AChE specifically in the skeletal muscle, display no growth deficit (Camp et al. 2008; Bernard et al. 2011).…”

Section: Discussionmentioning

confidence: 99%

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Near‐complete adaptation of the PRiMA knockout to the lack of central acetylcholinesterase

Farár

Mohr

Legrand

et al. 2012

Journal of Neurochemistry

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Acetylcholinesterase (AChE) rapidly hydrolyzes acetylcholine. At the neuromuscular junction, AChE is mainly anchored in the extracellular matrix by the collagen Q, whereas in the brain, AChE is tethered by the proline-rich membrane anchor (PRiMA).The AChE-deficient mice, in which AChE has been deleted from all tissues, have severe handicaps. Surprisingly, PRiMA KO mice in which AChE is mostly eliminated from the brain show very few deficits. We now report that most of the changes observed in the brain of AChE-deficient mice, and in particular the high levels of ambient extracellular acetylcholine and the massive decrease of muscarinic receptors, are also observed in the brain of PRiMA KO. However, the two groups of mutants differ in their responses to AChE inhibitors. Since PRiMA-KO mice and AChE-deficient mice have similar low AChE concentrations in the brain but differ in the AChE content of the peripheral nervous system, these results suggest that peripheral nervous system AChE is a major target of AChE inhibitors, and that its absence in AChE-deficient mice is the main cause of the slow development and vulnerability of these mice. At the level of the brain, the adaptation to the absence of AChE is nearly complete.

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Section: Discussionmentioning

confidence: 99%

“…In the NMJ, most of the AChE is anchored in the subsynaptic domains of the basal lamina by collagen Q (ColQ) (Krejci et al. 1997; Bernard et al. 2011).…”

mentioning

confidence: 99%

Near‐complete adaptation of the PRiMA knockout to the lack of central acetylcholinesterase

Farár

Mohr

Legrand

et al. 2012

Journal of Neurochemistry

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“…These bind to ColQ at the NMJ to make “asymmetric” AChE forms (Hall, 1973; Sanes and Hall, 1979; Krejci et al, 1997). Mice lacking ColQ fail to localize AChE at the NMJ (Feng et al, 1999; Bernard et al, 2011). NMJs still form, however, albeit with slightly aberrant shape, and animals are born and survive for at least several weeks, with 10–20% surviving for up to three months (Feng et al, 1999).…”

Section: The Synaptic Collagens – Maturation Of the Synapsementioning

confidence: 99%

Role of extracellular matrix proteins and their receptors in the development of the vertebrate neuromuscular junction

Singhal

Martin

2011

Developmental Neurobiology

123

107

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The vertebrate neuromuscular junction remains the best-studied model for understanding the mechanisms involved in synaptogenesis, due to its relatively large size, its simplicity of patterning and its unparalleled experimental accessibility. During neuromuscular development, each skeletal myofiber secretes and deposits around its extracellular surface an assemblage of extracellular matrix (ECM) proteins that ultimately form a basal lamina. This is also the case at the neuromuscular junction, where the motor nerve contributes additional factors. Before most of the current molecular components were known, it was clear that the synaptic ECM of adult skeletal muscles was unique in composition and contained factors sufficient to induce the differentiation of both pre- and postsynaptic membranes. Biochemical, genetic and microscopy studies have confirmed that agrin, laminin (221, 421, and 521), collagen IV (α3-α6), collagen XIII, perlecan and the ColQ-bound form of acetylcholinesterase are all synaptic ECM proteins with important roles in neuromuscular development. The roles of their many potential receptors and/or binding proteins has been more difficult to assess at the genetic level due to the complexity of membrane interactions with these large proteins, but roles for MuSK-LRP4 in agrin signaling and for integrins, dystroglycan, and voltage-gated calcium channels in laminin-dependent phenotypes have been identified. Synaptic extracellular matrix proteins and their receptors are involved in almost all aspects of synaptic development, including synaptic initiation, topography, ultrastructure, maturation, stability and transmission.

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“…For example, an upstream intron selectively controls expression in skeletal muscle (Camp et al, 2008(Camp et al, , 2010, and an alternatively spliced sequence influences the processing of AChE in CNS areas such as the striatum. The accessible gene product found in erythrocytes is not necessarily influenced by this intron or the splice option expressed primarily in brain (Dobbertin et al, 2009;Bernard et al, 2011). On the other hand, the nonsynonymous cSNP found in the open-reading frame of the gene and reflected in a change in stability of the gene product can be expected to influence expression, activity, and turnover of the enzyme in all regions of the central, autonomic and somatic motor nervous systems.…”

Section: Human Cholinesterase Variants and Cardiovascular Function 131mentioning

confidence: 99%

Naturally Occurring Variations in the Human Cholinesterase Genes: Heritability and Association with Cardiovascular and Metabolic Traits

Valle¹,

Radić²,

Rana³

et al. 2011

J Pharmacol Exp Ther

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Cholinergic neurotransmission in the central and autonomic nervous systems regulates immediate variations in and longerterm maintenance of cardiovascular function with acetylcholinesterase (AChE) activity that is critical to temporal responsiveness. Butyrylcholinesterase (BChE), largely confined to the liver and plasma, subserves metabolic functions. AChE and BChE are found in hematopoietic cells and plasma, enabling one to correlate enzyme levels in whole blood with hereditary traits in twins. Using both twin and unrelated subjects, we found certain single nucleotide polymorphisms (SNPs) in the ACHE gene correlated with catalytic properties and general cardiovascular functions. SNP discovery from ACHE resequencing identified 19 SNPs: 7 coding SNPs (cSNPs), of which 4 are nonsynonymous, and 12 SNPs in untranslated regions, of which 3 are in a conserved sequence of an upstream intron. Both AChE and BChE activity traits in blood were heritable: AChE at 48.8 Ϯ 6.1% and BChE at 81.4 Ϯ 2.8%. Allelic and haplotype variations in the ACHE and BCHE genes were associated with changes in blood AChE and BChE activities. AChE activity was associated with BP status and SBP, whereas BChE activity was associated with features of the metabolic syndrome (especially body weight and BMI). Gene products from cDNAs with nonsynonymous cSNPs were expressed and purified. Protein expression of ACHE nonsynonymous variant D134H (SNP6) is impaired: this variant shows compromised stability and altered rates of organophosphate inhibition and oxime-assisted reactivation. A substantial fraction of the D134H instability could be reversed in the D134H/R136Q mutant. Hence, common genetic variations at ACHE and BCHE loci were associated with changes in corresponding enzymatic activities in blood.

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Distinct localization of collagen Q and PRiMA forms of acetylcholinesterase at the neuromuscular junction

Cited by 30 publications

References 46 publications

Near‐complete adaptation of the PRiMA knockout to the lack of central acetylcholinesterase

Near‐complete adaptation of the PRiMA knockout to the lack of central acetylcholinesterase

Role of extracellular matrix proteins and their receptors in the development of the vertebrate neuromuscular junction

Naturally Occurring Variations in the Human Cholinesterase Genes: Heritability and Association with Cardiovascular and Metabolic Traits

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