title: Synaptic basal lamina-associated congenital myasthenic syndromes.
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.
authors.affiliation: Department of Neurology, University of California, Davis, California, USA. ramaselli@ucdavis.edu
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Maselli
authors.forename: Juan
authors.initials: J
authors.lastname: Arredondo
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ferns
authors.forename: Robert L
authors.initials: RL
authors.lastname: Wollmann
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism; D018171:Agrin / Q000235:genetics; D000818:Animals; D001485:Basement Membrane / Q000378:metabolism / Q000503:physiopathology*; D003094:Collagen / Q000235:genetics; D006801:Humans; D007797:Laminin / Q000235:genetics; D051379:Mice; D009045:Motor Endplate / Q000201:enzymology; D009124:Muscle Proteins / Q000235:genetics; D009154:Mutation; D020294:Myasthenic Syndromes, Congenital / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D009469:Neuromuscular Junction / Q000378:metabolism; D011485:Protein Binding; D013569:Synapses / Q000378:metabolism*
chemical_list: D018171:Agrin; D007797:Laminin; D009124:Muscle Proteins; C058783:laminin beta2; D003094:Collagen; D000110:Acetylcholinesterase; C114027:COLQ protein, human