Burgess R W, Nguyen Q T, Son Y J, Lichtman J W, Sanes J R
Department of Anatomy and Neurobiology, Washington University Medical School, St. Louis, Missouri 63110, USA.
Neuron. 1999 May;23(1):33-44. doi: 10.1016/s0896-6273(00)80751-5.
Agrin induces synaptic differentiation at the skeletal neuromuscular junction (NMJ); both pre- and postsynaptic differentiation are drastically impaired in its absence. Multiple alternatively spliced forms of agrin that differ in binding characteristics and bioactivity are synthesized by nerve and muscle cells. We used surgical chimeras, isoform-specific mutant mice, and nerve-muscle cocultures to determine the origins and nature of the agrin required for synaptogenesis. We show that agrin containing Z exons (Z+) is a critical nerve-derived inducer of postsynaptic differentiation, whereas neural isoforms containing a heparin binding site (Y+) and all muscle-derived isoforms are dispensable for major steps in synaptogenesis. Our results also suggest that the requirement of agrin for presynaptic differentiation is mediated indirectly by its ability to promote postsynaptic production or localization of appropriate retrograde signals.
聚集蛋白可诱导骨骼肌神经肌肉接头（NMJ）处的突触分化；若缺乏聚集蛋白，突触前和突触后的分化都会严重受损。神经细胞和肌肉细胞会合成多种具有不同结合特性和生物活性的可变剪接形式的聚集蛋白。我们利用手术嵌合体、亚型特异性突变小鼠以及神经 - 肌肉共培养来确定突触形成所需聚集蛋白的来源和性质。我们发现含有Z外显子（Z +）的聚集蛋白是突触后分化的关键神经源性诱导因子，而含有肝素结合位点的神经亚型（Y +）以及所有肌肉源性亚型对于突触形成的主要步骤来说并非必需。我们的结果还表明，聚集蛋白对突触前分化的需求是通过其促进突触后产生或定位适当逆行信号的能力间接介导的。
