Wild Franziska, Khan Muzamil Majid, Rudolf Rüdiger
a Institute of Molecular and Cell Biology, Mannheim University of Applied Sciences , Mannheim , Germany.
b Interdisciplinary Center for Neurosciences, Heidelberg University , Heidelberg , Germany.
Small GTPases. 2019 Sep;10(5):395-402. doi: 10.1080/21541248.2017.1324939. Epub 2017 Jun 8.
Vertebrate skeletal muscle contraction is mediated by nicotinic acetylcholine receptors (CHRN). Endocytosis and recycling of CHRN regulate their proper abundance at nerve-muscle synapses, i.e. neuromuscular junctions. Recent work showed that RAB5 is essential for CHRN endocytosis. Here, using in vivo-imaging of endocytosed CHRN and RAB-GFP fusion proteins, we deliver evidence for differential effects of RAB5-GFP, RAB4-GFP, and RAB11-GFP on CHRN endocytosis. Furthermore, while newly endocytosed CHRN colocalized with RAB5-GFP over large stretches of muscle fibers, RAB4-GFP and RAB11-GFP colocalized with endocytosed CHRN almost exclusively at neuromuscular junctions. In agreement with previous findings, this data suggests the existence of a specialized subsynaptic zone that is particularly relevant for CHRN recycling.
脊椎动物骨骼肌收缩由烟碱型乙酰胆碱受体(CHRN)介导。CHRN的内吞作用和再循环调节其在神经肌肉突触(即神经肌肉接头)处的适当丰度。最近的研究表明,RAB5对CHRN内吞作用至关重要。在此,通过对内吞的CHRN和RAB-GFP融合蛋白进行体内成像,我们提供了RAB5-GFP、RAB4-GFP和RAB11-GFP对CHRN内吞作用产生不同影响的证据。此外,虽然新内吞的CHRN在大片肌纤维上与RAB5-GFP共定位,但RAB4-GFP和RAB11-GFP几乎仅在神经肌肉接头处与内吞的CHRN共定位。与先前的研究结果一致,该数据表明存在一个对CHRN再循环特别重要的特殊突触下区域。