Zimmermann J, Neuhuber W L, Raab M
Institut für Anatomie, Lehrstuhl I, Friedrich-Alexander-Universität, Krankenhausstr. 9, 91054, Erlangen, Germany.
Histochem Cell Biol. 2017 Aug;148(2):189-206. doi: 10.1007/s00418-017-1555-7. Epub 2017 Mar 23.
Homer1, a scaffolding protein of the postsynaptic density (PSD), enriched at excitatory synapses is known to anchor and modulate group I metabotropic glutamate receptors (mGluRs) and different channel- and receptor-proteins. Homer proteins are expressed in neurons of different brain regions, but also in non-neuronal tissues like skeletal muscle. Occurrence and location of Homer1 and mGluR5 in myenteric plexus and neuromuscular junctions (NMJ) of rat esophagus have yet not been characterized. We located Homer1 and mGluR5 immunoreactivity (-iry) in rat esophagus and focused on myenteric neurons, intraganglionic laminar endings (IGLEs) and NMJs, using double- and triple-label immunohistochemistry and confocal laser scanning microscopy. Homer1-iry was found in a subpopulation of vesicular glutamate transporter 2 (VGLUT2) positive IGLEs and cholinergic varicosities within myenteric ganglia, but neither in nitrergic nor cholinergic myenteric neuronal cell bodies. Homer1-iry was detected in 63% of esophageal and, for comparison, in 35% of sternomastoid NMJs. Besides the location in the PSD, Homer1-iry colocalized with cholinergic markers, indicating a presynaptic location in coarse VAChT/CGRP/NF200- immunoreactive (-ir) terminals of nucleus ambiguus neurons supplying striated esophageal muscle. mGluR5-iry was found in subpopulations of myenteric neuronal cell bodies, VGLUT2-ir IGLEs and cholinergic varicosities within the myenteric neuropil and NMJs of esophagus and sternomastoid muscles. Thus, Homer1 may anchor mGluR5 at presynaptic sites of cholinergic boutons at esophageal motor endplates, in a small subpopulation of VGLUT2-ir IGLEs and cholinergic varicosities within myenteric ganglia possibly modulating Ca-currents and neurotransmitter release.
荷马1(Homer1)是突触后致密区(PSD)的一种支架蛋白,在兴奋性突触中富集,已知其可锚定并调节I型代谢型谷氨酸受体(mGluRs)以及不同的通道蛋白和受体蛋白。荷马蛋白在不同脑区的神经元中表达,但在骨骼肌等非神经组织中也有表达。大鼠食管肌间神经丛和神经肌肉接头(NMJ)中荷马1和mGluR5的存在情况及定位尚未明确。我们利用双重和三重标记免疫组织化学以及共聚焦激光扫描显微镜,在大鼠食管中定位了荷马1和mGluR5免疫反应性(-iry),并聚焦于肌间神经元、神经节内板层终末(IGLEs)和神经肌肉接头。在肌间神经节内的小泡型谷氨酸转运体2(VGLUT2)阳性IGLEs和胆碱能曲张体亚群中发现了荷马1-iry,但在含氮能或胆碱能的肌间神经节神经元胞体中均未发现。在63%的食管神经肌肉接头中检测到了荷马1-iry,作为对比,在35%的胸锁乳突肌神经肌肉接头中也检测到了。除了在PSD中的定位外,荷马1-iry还与胆碱能标记物共定位,表明在支配食管横纹肌的疑核神经元的粗大囊泡乙酰胆碱转运体/降钙素基因相关肽/神经丝蛋白200免疫反应性(-ir)终末中有突触前定位。在食管和胸锁乳突肌的肌间神经节神经元胞体亚群、VGLUT2-ir IGLEs以及肌间神经毡和神经肌肉接头内的胆碱能曲张体中发现了mGluR5-iry。因此,荷马1可能在食管运动终板胆碱能突触前位点锚定mGluR5,在肌间神经节内一小部分VGLUT2-ir IGLEs和胆碱能曲张体中,可能调节钙电流和神经递质释放。