SEROTONIN-MEDIATED ENDOCYTOSIS OF APCAM - AN EARLY STEP OF LEARNING-RELATED SYNAPTIC GROWTH IN APLYSIA

SEROTONIN-MEDIATED ENDOCYTOSIS OF APCAM - AN EARLY STEP OF LEARNING-RELATED SYNAPTIC GROWTH IN APLYSIA
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DOI:
10.1126/science.1585177
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发表时间:
1992-05-01
期刊:
影响因子:
56.9
通讯作者:
KANDEL, ER
KANDEL, ER
中科院分区:
综合性期刊1区
文献类型:
--
作者:
BAILEY, CH;CHEN, M;KANDEL, ER

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在感觉和运动神经元的分离细胞培养物中,5-羟色胺诱导的突触功效的长期促进伴随着新突触连接的生长。这种生长与感觉神经元中的失智细胞粘附分子(apCAM)的下调有关。为了研究这种下调的机制,结合了薄层电子显微镜与免疫标记的金结合的单克隆抗体特异性apCAM。在1小时内,5-羟色胺导致感觉神经元表面膜上的金标记复合物密度降低50%。这种下调是通过异源的、蛋白质合成依赖性的内体途径激活来实现的,这导致apCAM的内化和表观降解。这种内化在感觉神经元的突起相互接触的部位特别突出,并可能在那里起作用,使通常抑制生长的突起与突起之间的接触不稳定。反过来,内吞激活可能导致膜成分重新分布到新突触形成的部位。
The long-term facilitation of synaptic efficacy that is induced by serotonin in dissociated cell cultures of sensory and motor neurons of Aplysia is accompanied by the growth of new synaptic connections. This growth is associated with a down-regulation in the sensory neuron of Aplysia cell adhesion molecules (apCAMs). To examine the mechanisms of this down-regulation, thin-section electron microscopy was combined with immunolabeling by gold-conjugated monoclonal antibodies specific to apCAM. Within 1 hour, serotonin led to a 50% decrease in the density of gold-labeled complexes at the surface membrane of the sensory neuron. This down-regulation was achieved by a heterologous, protein synthesis-dependent activation of the endosomal pathway, which leads to internalization and apparent degradation of apCAM. The internalization is particularly prominent at sites where the processes of the sensory neurons contact one another and may act there to destabilize process-to-process contacts that normally inhibit growth. In turn, the endocytic activation may lead to a redistribution of membrane components to sites where new synapses form.