Meyer G, Wallace B G
Department of Physiology and Biophysics, C240, University of Colorado Health Sciences Center, 4200 East Ninth Avenue, Denver, Colorado, 80262, USA.
Mol Cell Neurosci. 1998 Aug;11(5-6):324-33. doi: 10.1006/mcne.1998.0689.
During synaptogenesis at the vertebrate skeletal neuromuscular junction, acetylcholine receptors (AChRs) form high-density aggregates opposite the presynaptic terminal in response to nerve-derived agrin. Agrin has been shown to stimulate tyrosine phosphorylation of a muscle-specific receptor tyrosine kinase MuSK and of the AChR beta subunit, and tyrosine kinase inhibitors and a tyrosine kinase-deficient mutant of MuSK prevent AChR aggregation. To evaluate the role of tyrosine phosphorylation of the AChR beta subunit in receptor aggregation, we replaced all three putative cytoplasmic tyrosine residues of the AChR beta subunit with phenylalanine residues and expressed the mutant receptors in cultured myotubes. Upon agrin treatment, transfected myotubes formed AChR aggregates that contained receptors with mutant beta subunits. Thus, AChRs can be recruited into agrin-induced specializations by protein-protein interactions that do not depend on tyrosine phosphorylation of the AChR beta subunit.
在脊椎动物骨骼肌神经肌肉接头的突触发生过程中，乙酰胆碱受体（AChRs）会在神经源性聚集蛋白的作用下，在突触前终末的对面形成高密度聚集体。已表明聚集蛋白能刺激肌肉特异性受体酪氨酸激酶MuSK以及AChRβ亚基的酪氨酸磷酸化，而酪氨酸激酶抑制剂和MuSK的酪氨酸激酶缺陷型突变体可阻止AChR聚集。为了评估AChRβ亚基的酪氨酸磷酸化在受体聚集中的作用，我们将AChRβ亚基的所有三个假定的胞质酪氨酸残基替换为苯丙氨酸残基，并在培养的肌管中表达突变受体。经聚集蛋白处理后，转染的肌管形成了含有突变β亚基受体的AChR聚集体。因此，AChRs可通过不依赖于AChRβ亚基酪氨酸磷酸化的蛋白质 - 蛋白质相互作用被募集到聚集蛋白诱导的特化结构中。
