Synaptic basal lamina-associated congenital myasthenic syndromes

Ricardo A Maselli, Juan Arredondo, Michael J Ferns, Robert L. Wollmann

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Proteins associated with the basal lamina (BL) participate in complex signal transduction processes that are essential for the development and maintenance of the neuromuscular junction (NMJ). Most important junctional BL proteins are collagens, such as collagen IV (α3-6), collagen XIII, and ColQ; laminins; nidogens; and heparan sulfate proteoglycans, such as perlecan and agrin. Mice lacking Colq (Colq-/-), laminin β2 (Lamb2-/-), or collagen XIII (Col13a1-/-) show immature nerve terminals enwrapped by Schwann cell projections that invaginate into the synaptic cleft and decrease contact surface for neurotransmission. Human mutations in COLQ, LAMB2, and AGRN cause congenital myasthenic syndromes (CMSs) owing to deficiency of ColQ, laminin-β2, and agrin, respectively. In these syndromes the NMJ ultrastructure shows striking resemblance to that of mice lacking the corresponding protein; furthermore, the extracellular localization of mutant proteins may provide favorable conditions for replacement strategies based on gene therapy and stem cells.

Original languageEnglish (US)
Pages (from-to)36-48
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume1275
Issue number1
DOIs
StatePublished - Dec 2012

Keywords

  • Agrin
  • Basal lamina
  • ColQ
  • Congenital myasthenic syndromes
  • Laminin β

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science

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