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Synaptic basal lamina–associated congenital myasthenic syndromes
Author(s) -
Maselli Ricardo A.,
Arredondo Juan,
Ferns Michael J.,
Wollmann Robert L.
Publication year - 2012
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2012.06807.x
Subject(s) - agrin , basal lamina , perlecan , laminin , neuromuscular junction , microbiology and biotechnology , extracellular matrix , heparan sulfate , biology , neuroscience , acetylcholine receptor , chemistry , anatomy , ultrastructure , biochemistry , glycosaminoglycan , proteoglycan , receptor
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.