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在缺乏基质金属蛋白酶-9的情况下,视觉皮层中细胞间粘附分子5(端脑连蛋白)的亚细胞定位不受发育调控。

Subcellular localization of intercellular adhesion molecule-5 (telencephalin) in the visual cortex is not developmentally regulated in the absence of matrix metalloproteinase-9.

作者信息

Kelly Emily A, Tremblay Marie-Eve, Gahmberg Carl G, Tian Li, Majewska Ania K

机构信息

Department of Neurobiology and Anatomy, University of Rochester, Rochester, New York, 14642.

出版信息

J Comp Neurol. 2014 Feb 15;522(3):676-88. doi: 10.1002/cne.23440.

Abstract

The telencephalon-associated intercellular adhesion molecule-5 (telencephalin; ICAM-5) regulates dendritic morphology in the developing brain. In vitro studies have shown that ICAM-5 is found predominantly within dendrites and immature dendritic protrusions, with reduced expression in mushroom spines, suggesting that ICAM-5 downregulation is critical for the maturation of synaptic structures. However, developmental expression of ICAM-5 has not been explored in depth at the ultrastructural level in intact brain tissue. To investigate the ultrastructural localization of ICAM-5 with transmission electron microscopy, we performed immunoperoxidase histochemistry for ICAM-5 in mouse visual cortex at postnatal day (P)14, a period of intense synaptogenesis, and at P28, when synapses mature. We observed the expected ICAM-5 expression in dendritic protrusions and shafts at both P14 and P28. ICAM-5 expression in these dendritic protrusions decreased in prevalence with developmental age to become localized predominantly to dendritic shafts by P28. To understand better the relationship between ICAM-5 and the endopeptidase metalloproteinase-9 (MMP-9), which mediates ICAM-5 cleavage following glutamate activation during postnatal development, we also explored ICAM-5 expression in MMP-9 null animals. This analysis revealed a similar expression of ICAM-5 in dendritic elements at P14 and P28; however, an increased prevalence of ICAM-5 was noted in dendritic protrusions at P28 in the MMP-9 null animals, indicating that, in the absence of MMP-9, there is no developmental shift in ICAM-5 subcellular localization. Our ultrastructural observations shed light on possible functions mediated by ICAM-5 and their regulation by extracellular proteases.

摘要

端脑相关细胞间黏附分子5(端脑素;ICAM - 5)在发育中的大脑中调节树突形态。体外研究表明,ICAM - 5主要存在于树突和未成熟的树突状突起中,在蘑菇状棘中的表达减少,这表明ICAM - 5的下调对于突触结构的成熟至关重要。然而,在完整脑组织的超微结构水平上,尚未深入研究ICAM - 5的发育表达。为了通过透射电子显微镜研究ICAM - 5的超微结构定位,我们在出生后第14天(P14)和P28(突触成熟时)对小鼠视觉皮层进行了ICAM - 5的免疫过氧化物酶组织化学检测。我们在P14和P28时均观察到树突状突起和树突干中有预期的ICAM - 5表达。随着发育年龄的增长,这些树突状突起中ICAM - 5的表达普遍性降低,到P28时主要定位于树突干。为了更好地理解ICAM - 5与内肽酶金属蛋白酶9(MMP - 9)之间的关系,MMP - 9在出生后发育过程中在谷氨酸激活后介导ICAM - 5的裂解,我们还研究了MMP - 9基因敲除动物中ICAM - 5的表达。该分析显示,在P14和P28时,树突成分中ICAM - 5的表达相似;然而,在MMP - 9基因敲除动物的P28树突状突起中,ICAM - 5的表达普遍性增加,这表明在没有MMP - 9的情况下,ICAM - 5亚细胞定位没有发育性转变。我们的超微结构观察揭示了ICAM - 5介导的可能功能及其受细胞外蛋白酶调节的情况。

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