ALCAM: Basis Sequence: Mouse.
ALCAM: Basis Sequence: Mouse.
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DOI：
10.1038/mp.a004126.01
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
Zijlstra, Andries
中科院分区：
文献类型：
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作者：
Hansen, Amanda G;Swart, Guido W;Zijlstra, Andries
ALCAM 作为细胞间粘附分子发挥作用，参与相邻细胞之间的同型 (ALCAM-ALCAM) 和异型 (ALCAM-CD6) 相互作用。这些相互作用是通过其最氨基末端的 V 结构域 (D1) 介导的。在 ALCAMALCAM 相互作用中，这似乎是 D1-D1 相互作用（Tanaka et al. 1991；van Kempen et al. 2001），而在 ALCAM-CD6 相互作用中，ALCAM D1 结构域与 CD6 的近膜清道夫受体富含半胱氨酸（SRCR）结构域结合（Bowen et al. 1996）。 ALCAM 还能够通过同一细胞中相邻 ALCAM 分子之间的横向相互作用进行寡聚化。这些相互作用通过膜附近的 D3-D5 结构域发生（van Kempen 等人，2001）。 ALCAM 表达在细胞与细胞接触的区域最为明显，它可能与其他细胞与细胞粘附分子相互作用。事实上，在前列腺癌细胞中，通过 α-N-连环蛋白转染重建 α-连环蛋白/E-钙粘蛋白复合物后，ALCAM 重新定位到细胞膜，并与 E-钙粘蛋白在细胞膜上共定位。此外，这些细胞恢复到上皮样形态（Tomita et al. 2000），进一步确定了 ALCAM 在细胞间粘附中的功能作用。氨基末端 V 型 Ig 结构域是细胞与细胞粘附相互作用所必需的，事实上，它表达为一种分离的、选择性剪接的异构体（Ikeda 和 Quertermous 2004）。虽然 ALCAM 参与多种生物过程已得到证实，但确切的分子机制仍不清楚。短胞质结构域的高度保守性表明 ALCAM 的功能部分是通过将细胞外信号传递到细胞质来实现的。尽管主要因其在白细胞中的作用而命名，但 ALCAM 表现出广泛的表达，包括神经元组织、上皮细胞和造血祖细胞。尽管 ALCAM 参与许多生物过程，但 ALCAM 基因敲除小鼠仍能存活、具有生育能力，并且没有外观可见的缺陷。对文献的全面分析需要考虑其所有替代名称，包括 CD166、MEMD、SC-1、BEN、GRASP、DM-GRASP、HCA 和 SB-10。
ALCAM functions as a cell–cell adhesion molecule and engages in homotypic (ALCAM–ALCAM) and heterotypic (ALCAM–CD6) interactions between adjacent cells. These interactions are mediated through its most amino-terminal V domain (D1). In ALCAMALCAM interactions this seems to be a D1–D1 interaction (Tanaka et al. 1991; van Kempen et al. 2001), while in ALCAM–CD6 interactions the ALCAM D1 domain binds to the membrane-proximal scavenger receptor cysteine rich (SRCR) domain of CD6 (Bowen et al. 1996). ALCAM is also capable of oligomerizing through lateral interactions between adjacent ALCAM molecules in the same cell. These interactions occur through the D3–D5 domains proximal to the membrane (van Kempen et al. 2001). ALCAM expression is most apparent at areas of cell–cell contact, where it may interact with other cell–cell adhesion molecules. In fact, upon reconstitution of the α-catenin/E-cadherin complex by α-N-catenin transfection, ALCAM relocalizes to the cell membrane and co-localizes with E-cadherin at the cell membrane in prostate cancer cells. In addition, these cells reverted to an epitheliallike morphology (Tomita et al. 2000) further defining a functional role for ALCAM in cell–cell adhesion. The amino-terminal V-type Ig domain is required for cell–cell adhesive interactions and is, in fact, expressed as an isolated, alternatively spliced isoform (Ikeda and Quertermous 2004).While the participation of ALCAM in several biological processes has been verified, the exact molecular mechanism remains unclear. The highly conserved nature of the short cytoplasmic domain suggests that ALCAM functions, in part, by conveying extracellular signals to the cytoplasm. Although named primarily for its role in leukocytes, ALCAM exhibits broad expression including neuronal tissues, epithelial cells, and hematopoietic progenitor cells. In spite of the participation of ALCAM in many biological processes, ALCAM knockout mice are viable, fertile and have no outward visible defects. A full analysis of the literature requires consideration of all its alternate names, including CD166, MEMD, SC-1, BEN, GRASP, DM-GRASP, HCA, and SB-10.