Fabre-Jonca N, Allaman J M, Radlgruber G, Meda P, Kiss J Z, French L E, Masson D
University of Geneva, Medical School, Switzerland.
Differentiation. 1998 Aug;63(4):169-80. doi: 10.1111/j.1432-0436.1998.00169.x.
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 E-MAP-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 apicobasal 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.
在间期细胞中，微管在细胞器和囊泡的细胞内分布及移动过程中发挥着重要作用，从而促进细胞极化和分化。微管的组织形式因细胞类型而异，推测是由组织特异性微管相关蛋白（MAPs）控制的。115 kDa的上皮MAP（E-MAP-115）已被鉴定为一种主要在上皮来源的细胞系中表达的微管稳定蛋白。为了评估E-MAP-115在体内上皮形态发生中的假定功能，我们克隆了编码小鼠蛋白的cDNA，并研究了E-MAP-115 mRNA和蛋白在小鼠胚胎发育过程及成年器官中的细胞分布。对小鼠E-MAP-115预测氨基酸序列的分析显示，它与其人类同源物有81%的序列同一性，该蛋白保守性最强的部分是微管结合位点。我们的数据表明，从胚胎发育9.5天起，E-MAP-115在多种上皮中表达，且其表达水平在发育过程中升高。从14.5天起，在一些神经元细胞中也能发现E-MAP-115 mRNA。在成年器官中，E-MAP-115在肾小管上皮细胞、肠吸收细胞中含量最为丰富，且在睾丸中广泛分布。E-MAP-115的表达与某些上皮细胞类型的分化相关：例如，在成年肠道中，E-MAP-115 mRNA和蛋白在分化细胞区室中比在增殖细胞区室中更为丰富。此外，E-MAP-115的表达明显与细胞顶-基极性程度相关。在发育中的肾脏中，在S形体、原始肾小管和肾小球的立方体细胞中可检测到E-MAP-115 mRNA，而在已失去初始顶-基极性的成熟足细胞中则不存在E-MAP-115 mRNA和蛋白。到目前为止，E-MAP-115在体内的分布模式对于一种MAP来说是独一无二的。综上所述，我们的结果支持了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。
