[SMC] Molecular Analysis of a Congenital Myasthenic Syndrome Due to a Pathogenic Variant Affecting the C-Terminus of Col
-
Auteur du sujet - Ami(e) de Diamant
- Messages : 3084
- Enregistré le : 31 mai 2020 09:57
- 3
- Zodiaque :
- Âge : 20
- Contact :
[SMC] Molecular Analysis of a Congenital Myasthenic Syndrome Due to a Pathogenic Variant Affecting the C-Terminus of Col
Int J Mol Sci. 2023 Nov 11;24(22):16217. doi: 10.3390/ijms242216217.
ABSTRACT
Congenital Myasthenic Syndromes (CMSs) are rare inherited diseases of the neuromuscular junction characterized by muscle weakness. CMSs with acetylcholinesterase deficiency are due to pathogenic variants in COLQ, a collagen that anchors the enzyme at the synapse. The two COLQ N-terminal domains have been characterized as being biochemical and functional. They are responsible for the structure of the protein in the triple helix and the association of COLQ with acetylcholinesterase. To deepen the analysis of the distal C-terminal peptide properties and understand the CMSs associated to pathogenic variants in this domain, we have analyzed the case of a 32 year old male patient bearing a homozygote splice site variant c.1281 C > T that changes the sequence of the last 28 aa in COLQ. Using COS cell and mouse muscle cell expression, we show that the COLQ variant does not impair the formation of the collagen triple helix in these cells, nor its association with acetylcholinesterase, and that the hetero-oligomers are secreted. However, the interaction of COLQ variant with LRP4, a signaling hub at the neuromuscular junction, is decreased by 44% as demonstrated by in vitro biochemical methods. In addition, an increase in all acetylcholine receptor subunit mRNA levels is observed in muscle cells derived from the patient iPSC. All these approaches point to pathophysiological mechanisms essentially characterized by a decrease in signaling and the presence of immature acetylcholine receptors.
PMID:38003406 | PMC:PMC10671321 | DOI:10.3390/ijms242216217
Source: https://pubmed.ncbi.nlm.nih.gov/3800340 ... 8&v=2.18.0
Si vous appréciez notre travail, merci de nous soutenir un petit don en cliquant ICI
Pour obtenir la traduction en français,
cliquez sur le bouton situé dans la barre des menus en haut de cette page
Pour les donateurs, si cet article vous intéresse, nous pouvons faire l’acquisition d'un tiré-à-part.
Merci d'en faire la demande sur association.amis-modo@myasthenie.com
Bonne lecture...
Pour obtenir la traduction en français,
cliquez sur le bouton situé dans la barre des menus en haut de cette page
Pour les donateurs, si cet article vous intéresse, nous pouvons faire l’acquisition d'un tiré-à-part.
Merci d'en faire la demande sur association.amis-modo@myasthenie.com
Bonne lecture...