Kenific Candia M, Wittmann Torsten, Debnath Jayanta
Department of Pathology and Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94143, USA Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, CA 94143, USA.
Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA 94143, USA.
J Cell Sci. 2016 Oct 15;129(20):3685-3693. doi: 10.1242/jcs.188490. Epub 2016 Sep 26.
Autophagy, a pathway for lysosomal-mediated cellular degradation, has recently been described as a regulator of cell migration. Although the molecular mechanisms underlying autophagy-dependent motility are only beginning to emerge, new work demonstrates that selective autophagy mediated by the autophagy cargo receptor, NBR1, specifically promotes the dynamic turnover of integrin-based focal adhesion sites during motility. Here, we discuss the detailed mechanisms through which NBR1-dependent selective autophagy supports focal adhesion remodeling, and we describe the interconnections between this pathway and other established regulators of focal adhesion turnover, such as microtubules. We also highlight studies that examine the contribution of autophagy to selective degradation of proteins that mediate cellular tension and to integrin trafficking; these findings hint at further roles for autophagy in supporting adhesion and migration. Given the recently appreciated importance of selective autophagy in diverse cellular processes, we propose that further investigation into autophagy-mediated focal adhesion turnover will not only shed light onto how focal adhesions are regulated but will also unveil new mechanisms regulating selective autophagy.
自噬是一种由溶酶体介导的细胞降解途径,最近被描述为细胞迁移的调节因子。尽管自噬依赖性运动的分子机制才刚刚开始显现,但新的研究表明,由自噬货物受体NBR1介导的选择性自噬在运动过程中特异性地促进基于整合素的粘着斑的动态周转。在这里,我们讨论了NBR1依赖性选择性自噬支持粘着斑重塑的详细机制,并描述了该途径与其他已确立的粘着斑周转调节因子(如微管)之间的联系。我们还重点介绍了一些研究,这些研究探讨了自噬对介导细胞张力的蛋白质的选择性降解以及对整合素运输的贡献;这些发现暗示了自噬在支持粘附和迁移方面的进一步作用。鉴于最近认识到选择性自噬在多种细胞过程中的重要性,我们建议进一步研究自噬介导的粘着斑周转不仅将阐明粘着斑是如何被调节的,还将揭示调节选择性自噬的新机制。