Medical Faculty, Center for Molecular Medicine Cologne (CMMC), Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Institute for Biochemistry I, University of Cologne, Joseph-Stelzmann-Str. 52, 50931, Cologne, Germany,
Adv Exp Med Biol. 2014;773:491-504. doi: 10.1007/978-1-4899-8032-8_22.
Nesprins are a family of proteins that are primarily known for their localization along the nuclear envelope. Together with inner nuclear membrane SUN proteins, they form the core of the LINC (Linker of Nucleoskeleton and Cytoskeleton) complex that traverses both nuclear membranes to connect the cytoplasm and the nuclear interior. Based on their structure and interactions, Nesprins integrate the nucleus into the cytoskeleton of a cell. Mutations in Nesprins have been identified in a group of human diseases that have been summarized as laminopathies. Cellular functions of the Nesprins and recent studies on different cancer types additionally draw interest on Nesprins in the field of cancer research. Here we summarize recent findings about the structural arrangements of Nesprins along the nuclear envelope, and highlight Nesprin functions in basic cellular processes like maintenance of nuclear shape and size, and of nuclear and cellular or cytoskeletal organization, centrosomal positioning, cell migration, and signal transduction. In summary, Nesprins are involved in critical cellular processes, which in case of malfunction contribute to the formation of cancer and might represent novel targets in cancer diagnosis or for therapeutic intervention.
nesprins 是一类主要定位于核膜的蛋白家族。它们与核膜内层 SUN 蛋白一起,构成了连接核膜内外、连接细胞质和核内的 LINC(核骨架和细胞骨架连接)复合物的核心。根据它们的结构和相互作用,nesprins 将细胞核整合到细胞的细胞骨架中。在一组被总结为 laminopathies 的人类疾病中,已经发现了 nesprins 的突变。nesprins 在不同癌症类型中的细胞功能和最近的研究也引起了癌症研究领域对 nesprins 的兴趣。在这里,我们总结了 nesprins 沿核膜的结构排列的最新发现,并强调了 nesprin 在维持核形状和大小、核和细胞或细胞骨架组织、中心体定位、细胞迁移和信号转导等基本细胞过程中的功能。总之,nesprins 参与了关键的细胞过程,在功能失调的情况下会导致癌症的形成,并且可能成为癌症诊断或治疗干预的新靶点。