Primary structure of a collagenic tail peptide of Torpedo acetylcholinesterase: co-expression with catalytic subunit induces the production of collagen-tailed forms in transfected cells.

Krejci, Éric; Coussen, Françoise; Duval, Nathalie; Châtel, Jean-Marc; Legay, Claire; Puype, Magda; Vandekerckhove, Joël; Cartaud, Jean; Bon, Suzanne; Massoulié, Jean

doi:10.1002/j.1460-2075.1991.tb08070.x

Cited by 138 publications

(90 citation statements)

References 42 publications

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“…In contrast, slow twitch muscles contain A 8 and A 4 forms that possess ColQ-1 subunit and are relatively abundant in the extra-junctional regions of muscle fibers as well as at the nmjs (2,21). The assembly, processing, and externalization of collagen-tailed AChE forms do not depend on a specialized post-synaptic apparatus and can occur in non-specialized cells (4,45). The ColQ-1 and ColQ-1a proteins differ essentially in their signal sequences and a few amino acids in their N termini (see Fig.…”

Section: Fig 8 Mutation Of the Nfat Motif Of Pcolq-1 Blocks Its Fibmentioning

confidence: 99%

“…Although the ColQ-1 promoter, which drives the expression of ColQ-1 in slow muscles, also contains N-box element, the ColQ-1-containing A 8 and A 4 form AChE are found extra-junctionally in slow muscles. Two possible reasons could account for this discrepancy.…”

Section: Fig 8 Mutation Of the Nfat Motif Of Pcolq-1 Blocks Its Fibmentioning

confidence: 99%

“…AChE T catalytic subunits produce amphiphilic monomers and dimers and nonamphiphilic homotetramers as well as heteromeric associations with anchoring proteins, ColQ and PRiMA, which allow their functional localization in cholinergic synapses (2). Collagen ColQ thus characterizes the collagen-tailed forms (A forms) of AChE and butyrylcholinesterase (3)(4)(5), which are localized in the basal lamina at neuromuscular junctions (nmjs) of vertebrates (6,7); in these molecules (A 4 , A 8 , A 12 ), one, two, or three tetramers of catalytic subunits are disulfide-linked to the strands of a triple helix of ColQ collagen. The cDNAs encoding ColQ have been cloned in Torpedo and mammals (4,8,9).…”

mentioning

confidence: 99%

“…Collagen ColQ thus characterizes the collagen-tailed forms (A forms) of AChE and butyrylcholinesterase (3)(4)(5), which are localized in the basal lamina at neuromuscular junctions (nmjs) of vertebrates (6,7); in these molecules (A 4 , A 8 , A 12 ), one, two, or three tetramers of catalytic subunits are disulfide-linked to the strands of a triple helix of ColQ collagen. The cDNAs encoding ColQ have been cloned in Torpedo and mammals (4,8,9). The primary structure of ColQ comprises a signal peptide, an N-terminal domain containing a proline-rich motif (PRAD) that associates with four C-terminal T peptides of AChE T or butyrylcholinesterase subunits, a collagenous domain with characteristic repeats of glycines every three residues, and a C-terminal region (10,11).…”

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confidence: 99%

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Transcriptional Regulation of Acetylcholinesterase-associated Collagen ColQ

Lee

Choi

Ting

et al. 2004

Journal of Biological Chemistry

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The presence of a collagenous protein (ColQ) characterizes the collagen-tailed forms of acetylcholinesterase and butyrylcholinesterase at vertebrate neuromuscular junctions which is tethered in the synaptic basal lamina. ColQ subunits, differing mostly by their signal sequences, are encoded by transcripts ColQ-1 and ColQ-1a, which are differentially expressed in slow and fast twitch muscles in mammals. Two distinct promoters, pColQ-1 and pColQ-1a, were isolated from the upstream sequences of human COLQ gene; they showed musclespecific expression and were activated by myogenic transcriptional elements in cultured myotubes. After in vivo DNA transfection, pColQ-1 showed strong activity in slow twitch muscle (e.g. soleus), whereas pColQ-1a was preferably expressed in fast twitch muscle (e.g. tibialis). Mutation analysis of the ColQ promoters suggested that the muscle fiber type-specific expression pattern of ColQ transcripts were regulated by a slow upsteam regulatory element (SURE) and a fast intronic regulatory element (FIRE). These regulatory elements were responsive to a calcium ionophore and to calcineurin inhibition by cyclosporine A. The slow fiber type-specific expression of ColQ-1 was abolished by the mutation of an NFAT element in pColQ-1. Moreover, both the ColQ promoters contained N-box element that was responsible for the synapse-specific expression of ColQ transcripts. These results explain the specific expression patterns of collagen-tailed acetylcholinesterase in slow and fast muscle fibers.

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Section: Fig 8 Mutation Of the Nfat Motif Of Pcolq-1 Blocks Its Fibmentioning

confidence: 99%

Section: Fig 8 Mutation Of the Nfat Motif Of Pcolq-1 Blocks Its Fibmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Transcriptional Regulation of Acetylcholinesterase-associated Collagen ColQ

Lee

Choi

Ting

et al. 2004

Journal of Biological Chemistry

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“…1A). Each N-terminal domain organizes an AChE tetramer, so the triple-helical structure generates an A 12 or asymmetric AChE form with 12 catalytic subunits (3,4). The collagen domain is characterized by Gly-Xaa-Yaa repeats and a high proportion of the stabilizing proline and hydroxyproline residues.…”

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confidence: 99%

Two Different Heparin-binding Domains in the Triple-helical Domain of ColQ, the Collagen Tail Subunit of Synaptic Acetylcholinesterase

Deprez

Inestrosa

Krejci

2003

Journal of Biological Chemistry

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ColQ, the collagen tail subunit of asymmetric acetylcholinesterase, is responsible for anchoring the enzyme at the vertebrate synaptic basal lamina by interacting with heparan sulfate proteoglycans. To get insights about this function, the interaction of ColQ with heparin was analyzed. For this, heparin affinity chromatography of the complete oligomeric enzyme carrying different mutations in ColQ was performed. Results demonstrate that only the two predicted heparin-binding domains present in the collagen domain of ColQ are responsible for heparin interaction. Despite their similarity in basic charge distribution, each heparin-binding domain had different affinity for heparin. This difference is not solely determined by the number or nature of the basic residues conforming each site, but rather depends critically on local structural features of the triple helix, which can be influenced even by distant regions within ColQ. Thus, ColQ possesses two heparinbinding domains with different properties that may have non-redundant functions. We hypothesize that these binding sites coordinate acetylcholinesterase positioning within the organized architecture of the neuromuscular junction basal lamina.At vertebrate cholinergic synapses, acetylcholinesterase (AChE) 1 rapidly hydrolyzes the neurotransmitter acetylcholine, thereby terminating synaptic transmission. This key function does not only require a high catalytic turnover number but also a strategic positioning of the enzyme. This is achieved by the association of AChE catalytic subunits with structural subunits that bring them to the site of action. In the case of asymmetric AChE, the collagen ColQ is responsible for the localization of the enzyme at the vertebrate neuromuscular junction. Inactivation of the ColQ gene in mice or mutations in the human ColQ gene result in the absence of enzyme accumulation at the neuromuscular junction and are the cause of a congenital myasthenic syndrome (type 1c) (1, 2).As found in other collagens, ColQ contains a central triplehelical domain surrounded by non-collagenous N-and C-terminal domains (Fig. 1A). Each N-terminal domain organizes an AChE tetramer, so the triple-helical structure generates an A 12 or asymmetric AChE form with 12 catalytic subunits (3, 4). The collagen domain is characterized by Gly-Xaa-Yaa repeats and a high proportion of the stabilizing proline and hydroxyproline residues. The C-terminal domain is divided into a proline-rich region, important for triple-helix formation (5), and a cysteinerich region probably involved in the anchorage of AChE at the neuromuscular junction, since mutations in this region prevent the accumulation of AChE in congenital myasthenic syndrome type 1c patients (2).Heparan sulfate proteoglycans (HSPGs) have been implicated in the anchorage of asymmetric AChE to the synaptic basal lamina by interacting with ColQ through their heparan sulfate (HS) chains. This was proposed after showing that AChE could be specifically solubilized from the tissue with heparinase as well as with HS and ...

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Congenital Myasthenic Syndromes

Engel¹,

Ohno²,

Sine³

1999

Arch Neurol

104

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Congenital myasthenic syndromes (CMS) can arise from presynaptic, synaptic, or postsynaptic defects. Mutations of the acetylcholine receptor (AChR) that increase or decrease the synaptic response to acetylcholine (ACh) are a common cause of the postsynaptic CMS. An increased response occurs in the slow-channel syndromes. Here, dominant mutations in different AChR subunits and in different domains of the subunits prolong the activation episodes of AChR by either delaying channel closure or increasing the affinity of AChR for ACh. A decreased synaptic response to ACh occurs with recessive, loss-of-function mutations. Missense mutations in the low-affinity, fast-channel syndrome and in a disorder associated with mode-switching kinetics of AChR result in brief activation episodes and reduce the probability of channel opening. Mutations causing premature termination of the translational chain or missense mutations preventing the assembly or glycosylation of AChR curtail the expression of AChR. These mutations are concentrated in the epsilon subunit, probably because substitution of the fetal gamma for the adult epsilon subunit can rescue humans from fatal null mutations in epsilon. Recent molecular genetic studies have also elucidated the pathogenesis of the CMS caused by absence of the asymmetric form of acetylcholinesterase from the synaptic basal lamina. Endplate acetylcholinesterase deficiency is now known to be caused by mutations in the collagenic tail subunit of the asymmetric enzyme that prevents the association of the collagenic tail subunit with the catalytic subunit or its insertion into the basal lamina.

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Primary structure of a collagenic tail peptide of Torpedo acetylcholinesterase: co-expression with catalytic subunit induces the production of collagen-tailed forms in transfected cells.

Cited by 138 publications

References 42 publications

Transcriptional Regulation of Acetylcholinesterase-associated Collagen ColQ

Transcriptional Regulation of Acetylcholinesterase-associated Collagen ColQ

Two Different Heparin-binding Domains in the Triple-helical Domain of ColQ, the Collagen Tail Subunit of Synaptic Acetylcholinesterase

Congenital Myasthenic Syndromes

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