Polo-Parada L, Bose C M, Landmesser L T
Department of Neurosciences, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
Neuron. 2001 Dec 6;32(5):815-28. doi: 10.1016/s0896-6273(01)00521-9.
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.
尽管在缺乏神经细胞黏附分子（NCAM）的小鼠中形成了功能性神经肌肉接头（NMJ），但它们在突触前组织和功能方面表现出多种改变。重复刺激时出现的深度抑制和异常的周期性完全传递失败表明囊泡动员/循环存在缺陷，并且在（+/+）NMJ中，已知影响囊泡动员的肌球蛋白轻链激酶抑制剂可模拟这些缺陷。利用不同内吞机制和Ca(2+)通道的两种独立释放机制在（-/-）终末中共存，成熟过程靶向与肌肉相对的突触前膜，而异常保留的未成熟过程靶向突触前终末和轴突的其余部分。因此，NCAM在突触前NMJ的分子组织中起着关键且迄今未被怀疑的作用。
