DiGiacomo Vincent, Meruelo Daniel
Department of Pathology, New York University School of Medicine, 180 Varick Street, New York, NY 10014, U.S.A.
NYU Cancer Institute, 550 First Avenue, New York, NY 10016, U.S.A.
Biol Rev Camb Philos Soc. 2016 May;91(2):288-310. doi: 10.1111/brv.12170. Epub 2015 Jan 28.
The 37/67-kDa laminin receptor (LAMR/RPSA) was originally identified as a 67-kDa binding protein for laminin, an extracellular matrix glycoprotein that provides cellular adhesion to the basement membrane. LAMR has evolutionary origins, however, as a 37-kDa RPS2 family ribosomal component. Expressed in all domains of life, RPS2 proteins have been shown to have remarkably diverse physiological roles that vary across species. Contributing to laminin binding, ribosome biogenesis, cytoskeletal organization, and nuclear functions, this protein governs critical cellular processes including growth, survival, migration, protein synthesis, development, and differentiation. Unsurprisingly given its purview, LAMR has been associated with metastatic cancer, neurodegenerative disease and developmental abnormalities. Functioning in a receptor capacity, this protein also confers susceptibility to bacterial and viral infection. LAMR is clearly a molecule of consequence in human disease, directly mediating pathological events that make it a prime target for therapeutic interventions. Despite decades of research, there are still a large number of open questions regarding the cellular biology of LAMR, the nature of its ability to bind laminin, the function of its intrinsically disordered C-terminal region and its conversion from 37 to 67 kDa. This review attempts to convey an in-depth description of the complexity surrounding this multifaceted protein across functional, structural and pathological aspects.
37/67 kDa层粘连蛋白受体（LAMR/RPSA）最初被鉴定为一种与层粘连蛋白结合的67 kDa蛋白，层粘连蛋白是一种细胞外基质糖蛋白，可使细胞粘附于基底膜。然而，LAMR在进化上起源于一种37 kDa的RPS2家族核糖体成分。RPS2蛋白在生命的所有领域都有表达，已被证明具有显著多样的生理作用，且因物种而异。这种蛋白有助于层粘连蛋白结合、核糖体生物合成、细胞骨架组织和核功能，它控制着包括生长、存活、迁移、蛋白质合成、发育和分化在内的关键细胞过程。鉴于其职责范围，LAMR与转移性癌症、神经退行性疾病和发育异常有关也就不足为奇了。作为一种受体发挥作用时，这种蛋白还会使人易受细菌和病毒感染。LAMR显然是人类疾病中的一个重要分子，直接介导病理事件，使其成为治疗干预的主要靶点。尽管经过了数十年的研究，但关于LAMR的细胞生物学、其结合层粘连蛋白的能力的本质、其内在无序的C末端区域的功能以及其从37 kDa转变为67 kDa等问题，仍有大量悬而未决。本综述试图从功能、结构和病理方面深入描述围绕这种多面蛋白的复杂性。
