ABERRANT DIFFERENTIATION OF NEUROMUSCULAR-JUNCTIONS IN MICE LACKING S-LAMININ LAMININ BETA-2
ABERRANT DIFFERENTIATION OF NEUROMUSCULAR-JUNCTIONS IN MICE LACKING S-LAMININ LAMININ BETA-2
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DOI：
10.1038/374258a0
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发表时间：
1995-03-16
期刊：
影响因子：
64.8
通讯作者：
MERLIE, JP
中科院分区：
文献类型：
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作者：
NOAKES, PG;GAUTAM, M;MERLIE, JP
突触的形成需要突触前和突触后伙伴之间复杂的信息交换。在骨骼神经肌肉接头处，这些信息中的一些包含在基底层（BL）中，基底层（BL）贯穿运动神经末梢和肌肉纤维之间的突触间隙。在损伤后的再生过程中，突触BL的成分可以在没有神经末梢的情况下触发突触后分化的几个特征，以及在没有肌纤维的情况下触发突触前分化的几个特征（1-3）。已知突触BL的一种神经源性成分聚集蛋白影响突触后分化3，但尚未显示肌肉源性成分影响运动神经末梢。这种作用的候选者是s-层粘连蛋白（也称为层粘连蛋白β 2），它是广泛分布的BL糖蛋白层粘连蛋白的B1（β 1）链的同源物（30）。s-层粘连蛋白由肌细胞合成（5）并集中在突触BL中（4）。在体外，重组s-层粘连蛋白片段选择性粘附运动神经元样细胞，抑制由其他基质分子促进的神经突生长，并作为生长神经突的“停止信号”（6，7）。通过产生和表征具有s-层粘连蛋白基因的靶向突变的小鼠，我们在这里表明s-层粘连蛋白调节运动神经末梢的形成。
SYNAPSE formation requires a complex interchange of information between the pre- and postsynaptic partners. At the skeletal neuromuscular junction, some of this information is contained in the basal lamina (BL), which runs through the synaptic cleft between the motor nerve terminal and the muscle fibre. During regeneration following injury, components of synaptic BL can trigger several features of postsynaptic differentiation in the absence of the nerve terminal, and of presynaptic differentiation in the absence of the muscle fibre(1-3). One nerve-derived component of synaptic BL, agrin, is known to affect postsynaptic differentiation3, but no muscle-derived components have yet been shown to influence motor nerve terminals. A candidate for such a role is s-laminin (also called laminin beta 2), a homologue of the B1 (beta 1) chain of the widely distributed BL glycoprotein, laminin(30). s-laminin is synthesized by muscle cells(5) and concentrated in synaptic BL(4). In vitro, recombinant s-laminin fragments are selectively adhesive for motor neuron-like cells, inhibit neurite outgrowth promoted by other matrix molecules, and act as a 'stop signal' for growing neurites(6,7). By generating and characterizing mice with a targeted mutation of the s-laminin gene, we show here that s-laminin regulates formation of motor nerve terminals.