title: Alterations in transmission, vesicle dynamics, and transmitter release machinery at NCAM-deficient neuromuscular junctions.
abstract: Although functional neuromuscular junctions (NMJs) form in NCAM-deficient mice, they exhibit multiple alterations in presynaptic organization and function. Profound depression and unusual periodic total transmission failures with repetitive stimulation point to a defect in vesicle mobilization/cycling, and these defects were mimicked in (+/+) NMJs by inhibitors of myosin light chain kinase, known to affect vesicle mobilization. Two separate release mechanisms, utilizing different endocytic machinery and Ca(2+) channels, were shown to coexist in (-/-) terminals, with the mature process targeted to presynaptic membrane opposed to muscle, and an abnormally retained immature process targeted to the remainder of the presynaptic terminal and axon. Thus, NCAM plays a critical and heretofore unsuspected role in the molecular organization of the presynaptic NMJ.
authors.affiliation: Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
authors.forename: L
authors.initials: L
authors.lastname: Polo-Parada
authors.forename: C M
authors.initials: CM
authors.lastname: Bose
authors.forename: L T
authors.initials: LT
authors.lastname: Landmesser
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism; D004558:Electric Stimulation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019006:Neural Cell Adhesion Molecules / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D009435:Synaptic Transmission / Q000235:genetics*; D013572:Synaptic Vesicles / Q000235:genetics / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D019006:Neural Cell Adhesion Molecules; D018377:Neurotransmitter Agents