The distribution of murine 115-kDa epithelial microtubule-associated protein (E-MAP-115) during embryogenesis and in adult organs suggests a role in epithelial polarization and differentiation

The distribution of murine 115-kDa epithelial microtubule-associated protein (E-MAP-115) during embryogenesis and in adult organs suggests a role in epithelial polarization and differentiation
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DOI:
10.1046/j.1432-0436.1998.6340169.x
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发表时间:
1998-08-01
期刊:
影响因子:
2.9
通讯作者:
Masson, D
Masson, D
中科院分区:
生物学3区
文献类型:
--
作者:
Fabre-Jonca, N;Allaman, JM;Masson, D

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在间期细胞中,微管在细胞器和囊泡的胞内分布和运动中起着至关重要的作用,从而有助于细胞的极化和分化。微管的组织随细胞类型而变化,可能是由组织特异性微管相关蛋白(MAPs)控制的。115-kDa上皮MAP (E-MAP-115)已被确定为微管稳定蛋白,主要在上皮来源的细胞系中表达。为了评估EMAP-115在体内上皮形态发生中的假设功能,我们克隆了编码该小鼠蛋白的cDNA,并研究了E-MAP-115 mRNA和蛋白在小鼠胚胎发生和成年器官中的细胞分布。对预测的鼠E-MAP-115氨基酸序列的分析显示,该蛋白与人类同源物的同源性为81%,其最保守的部分是微管结合位点。我们的数据表明,E-MAP-115从胚胎发生的9.5天起就在几个上皮细胞中表达,并且在发育过程中其表达水平增加。从14.5天开始,E-MAP-115 mRNA也在一些神经元细胞中被发现。在成人器官中,E-MAP-115在肾小管上皮细胞和肠吸收细胞中含量最多,并广泛分布于睾丸。E-MAP-115的表达与某些上皮细胞类型的分化相关:例如,在成人肠中,E-MAP-115 mRNA和蛋白在分化细胞区比在增殖细胞区更丰富。此外,E-MAP-115的表达与细胞顶基极性的程度明显相关。在发育中的肾脏中,E-MAP-115 mRNA在s形体的立方细胞、原始小管和肾小球中检测到,而E-MAP-115 mRNA和蛋白在成熟的足细胞中不存在,这些足细胞已经失去了最初的顶基极性。到目前为止,E-MAP-115在体内的分布模式对MAP来说是独一无二的。综上所述,我们的研究结果支持了E-MAP-115在上皮细胞极化和分化过程中重组微管细胞骨架的作用。
In interphase cells microtubules play fundamental roles in the intracellular distribution and movement of organelles and vesicles and thereby contribute to cellular polarization and differentiation. The organization of microtubules varies with the cell type and is presumably controlled by tissue-specific microtubule-associated proteins (MAPs). The 115-kDa epithelial MAP (E-MAP-115) has been identified as a microtubule-stabilizing protein predominantly expressed in cell lines of epithelial origin. To assess a putative function of EMAP-115 in epithelial morphogenesis in vivo, we have cloned the cDNA encoding the murine protein and studied the cellular distribution of E-MAP-115 mRNA and protein during murine embryogenesis and in adult organs. Analysis of the predicted amino acid sequence of murine E-MAP-115 revealed 81% sequence identity with its human homolog, the best-conserved part of the protein being the microtubule-binding site. Our data indicate that E-MAP-115 is expressed in several epithelia from 9.5 days of embryogenesis onwards and that its expression levels increase during development. From 14.5 days onwards, E-MAP-115 mRNA is found in some neuronal cells as well. In adult organs, E-MAP-115 is most abundant in epithelial cells of kidney tubules, in absorptive cells of the intestine and is widely distributed in the testis. E-MAP-115 expression correlates with the differentiation of certain epithelial cell types: in the adult intestine, for example, E-MAP-115 mRNA and protein are more abundant in the differentiating than in the proliferative cell compartment. Moreover, E-MAP-115 expression clearly correlates with the degree of cellular apico-basal polarity. In the developing kidney, E-MAP-115 mRNA is detected in the cuboidal cells of S-shaped bodies, of primitive tubules and glomerula, whereas, E-MAP-115 mRNA and protein are absent from mature podocytes which have lost their initial apico-basal polarity. The pattern of distribution of E-MAP-115 in vivo is so far unique for a MAP. Taken together, our results provide support for a role of E-MAP-115 in reorganizing the microtubule cytoskeleton during epithelial cell polarization and differentiation.