ARIA is concentrated in the synaptic basal lamina of the developing chick neuromuscular junction.

ARIA is concentrated in the synaptic basal lamina of the developing chick neuromuscular junction.
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ARIA集中在发育中的雏鸡神经肌肉连接的突触基底层中。

DOI:
10.1083/jcb.130.6.1423
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发表时间:
1995-09
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Fischbach GD
Fischbach GD
中科院分区:
其他
文献类型:
--
作者:
Goodearl AD;Yee AG;Sandrock AW Jr;Corfas G;Fischbach GD

文献摘要

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ARIA是多肽生长和分化因子家族的成员,其还包括神经胶质生长因子(GGF)、neu分化因子和调蛋白。ARIA mRNA在大鼠和鸡的中枢神经系统的所有胆碱能神经元中表达,包括脊髓运动神经元。在体外,ARIA提高了乙酰胆碱受体掺入鸡肌管原代培养物质膜的速率。为了研究ARIA是否可以调节鸡胚中连接突触乙酰胆碱受体的合成,我们开发了识别ARIA亚型的核糖探针和多克隆抗体试剂,其中包括氨基末端免疫球蛋白C2结构域,并研究了ARIA在运动神经元和神经肌肉接头中的表达和分布。早在胚胎第5天,我们就在运动神经元中检测到显著的ARIA mRNA表达,大约在运动轴突与其靶肌肉细胞进行初始突触接触的时候。在年龄较大的胚胎和出生后的动物中,我们发现ARIA蛋白集中在神经肌肉接头的突触间隙中,与运动轴突的运输和神经末梢的释放一致。在高分辨率使用免疫电子显微镜,我们检测到ARIA免疫反应性只在突触基底层的模式与结合到突触特异性成分的基底层的突触前侧。这些结果支持ARIA作为运动神经元末梢释放的营养因子的作用,其可以调节成熟神经肌肉突触的形成。
ARIA is a member of a family of polypeptide growth and differentiation factors that also includes glial growth factor (GGF), neu differentiation factor, and heregulin. ARIA mRNA is expressed in all cholinergic neurons of the central nervous systems of rats and chicks, including spinal cord motor neurons. In vitro, ARIA elevates the rate of acetylcholine receptor incorporation into the plasma membrane of primary cultures of chick myotubes. To study whether ARIA may regulate the synthesis of junctional synaptic acetylcholine receptors in chick embryos, we have developed riboprobes and polyclonal antibody reagents that recognize isoforms of ARIA that include an amino-terminal immunoglobulin C2 domain and examined the expression and distribution of ARIA in motor neurons and at the neuromuscular junction. We detected significant ARIA mRNA expression in motor neurons as early as embryonic day 5, around the time that motor axons are making initial synaptic contacts with their target muscle cells. In older embryos and postnatal animals, we found ARIA protein concentrated in the synaptic cleft at neuromuscular junctions, consistent with transport down motor axons and release at nerve terminals. At high resolution using immunoelectron microscopy, we detected ARIA immunoreactivity exclusively in the synaptic basal lamina in a pattern consistent with binding to synapse specific components on the presynaptic side of the basal lamina. These results support a role for ARIA as a trophic factor released by motor neuron terminals that may regulate the formation of mature neuromuscular synapses.