Werle M J, Sojka A M
Department of Anatomy and Cell Biology, Kansas University Medical Center, Kansas City 66160-7400, USA.
J Neurobiol. 1996 Jun;30(2):293-302. doi: 10.1002/(SICI)1097-4695(199606)30:2<293::AID-NEU10>3.0.CO;2-L.
The neuromuscular junction is a plastic structure and is constantly undergoing changes as the nerve terminals that innervate the muscle fiber extend and retract their processes. In vivo observations on developing mouse neuromuscular junctions revealed that prior to the retraction of a nerve terminal the acetylcholine receptors (AChRs) under that nerve terminal disperse. Agrin is a protein released by nerve terminals that binds to synaptic basal lamina and directs the aggregation of AChRs and acetylcholinesterase (AChE) in and on the surface of the myotube. Thus, if the AChRs under a nerve terminal disperse, then the cellular signaling mechanism by which agrin maintains the aggregation of those AChRs, must have been disrupted. Two possibilities that could lead to the disruption of the agrin induced aggregation are that agrin is present at the synaptic basal lamina but is unable to direct the aggregation of AChRs, or that agrin has been removed from the synaptic basal lamina. Thus, if agrin were blocked, one would expect to see anti-agrin staining at abandoned synaptic sites; whereas if agrin were removed, anti-agrin staining would be absent at abandoned synaptic sites. We find that anti-agrin staining and alpha-bungarotoxin staining are absent at abandoned synaptic sites. Further, in vivo observations of retracting nerve terminals confirm that agrin is removed from the synaptic basal lamina within 7 days. Thus, while agrin will remain bound to synaptic basal lamina for months following denervation, it is removed within days following synaptic retraction.
神经肌肉接头是一种可塑性结构，随着支配肌纤维的神经末梢伸展和缩回其突起，它不断发生变化。对发育中的小鼠神经肌肉接头的体内观察表明，在神经末梢缩回之前，该神经末梢下方的乙酰胆碱受体（AChRs）会分散。聚集蛋白是一种由神经末梢释放的蛋白质，它与突触基底层结合，并指导AChRs和乙酰胆碱酯酶（AChE）在肌管表面及其内部聚集。因此，如果神经末梢下方的AChRs分散，那么聚集蛋白维持这些AChRs聚集的细胞信号传导机制必定已被破坏。可能导致聚集蛋白诱导聚集破坏的两种可能性是，聚集蛋白存在于突触基底层，但无法指导AChRs的聚集，或者聚集蛋白已从突触基底层被移除。因此，如果聚集蛋白被阻断，人们会预期在废弃的突触位点看到抗聚集蛋白染色；而如果聚集蛋白被移除，在废弃的突触位点则不会有抗聚集蛋白染色。我们发现在废弃的突触位点没有抗聚集蛋白染色和α-银环蛇毒素染色。此外，对缩回神经末梢的体内观察证实，聚集蛋白在7天内从突触基底层被移除。因此，虽然去神经支配后聚集蛋白会在突触基底层结合数月，但在突触缩回后数天内它就会被移除。
