Lanuza M A, Li M X, Jia M, Kim S, Davenport R, Dunlap V, Nelson P G
Unitat díHistologia i Neurobiologia, Facultat Medicina i Ciencies de la Salut, Universitat Rovira i Virgili, Reus, Spain.
J Neurosci Res. 2000 Sep 15;61(6):616-25. doi: 10.1002/1097-4547(20000915)61:6<616::AID-JNR5>3.0.CO;2-N.
Activation of a mouse in vitro neuromuscular synapse produces a reduction in synaptic efficacy which is greater for nonactivated than for activated inputs to the myotubes. This has been shown to require thrombin and thrombin receptor activation and to involve a protein kinase C (PKC)-mediated step. We show in the present work that phorbol ester activation of PKC produces physiological loss of synapses in a time- and dose-related manner. We observe, using quantitative imaging methods, a parallel loss of acetylcholine receptors (AChR) from synaptically functional neurite-associated receptor aggregates in nerve-muscle cocultures. Biochemical measurements of total AChR show that PKC activation reduces both AChR stability (increases receptor loss) and receptor insertion into the surface membrane. Taken together, the data suggest that PKC activation decreases the stability of AChR aggregates in the muscle surface membrane. We conclude that PKC plays a crucial role in activity-dependent synapse reduction and does so, at least in part, by altering AChR stability.
激活小鼠体外神经肌肉突触会导致突触效能降低，对于肌管的未激活输入而言，这种降低比激活输入更为显著。这已被证明需要凝血酶和凝血酶受体激活，并涉及蛋白激酶C（PKC）介导的步骤。我们在当前研究中表明，PKC的佛波酯激活以时间和剂量相关的方式导致突触生理性丧失。我们使用定量成像方法观察到，在神经肌肉共培养物中，来自与突触功能相关的神经突相关受体聚集体的乙酰胆碱受体（AChR）平行丧失。对总AChR的生化测量表明，PKC激活会降低AChR稳定性（增加受体丧失）以及受体插入表面膜的能力。综合来看，数据表明PKC激活会降低肌肉表面膜中AChR聚集体的稳定性。我们得出结论，PKC在活性依赖性突触减少中起关键作用，并且至少部分是通过改变AChR稳定性来实现的。
