Alterations in transmission, vesicle dynamics, and transmitter release machinery at NCAM-deficient neuromuscular junctions.
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.
Polo-Parada
L
L
Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
Bose
C M
CM
Landmesser
L T
LT
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*
D015220:Calcium Channels; D019006:Neural Cell Adhesion Molecules; D018377:Neurotransmitter Agents