近日,哈尔滨工业大学生命科学学院合约研究员刘北东、博士生宋佳和杨晓雪关于SIR2基因的研究取得了重大成果,研究论文《细胞蛋白聚合体的隔离与细胞肌动蛋白和极化机制相关》发表在最新一期的《细胞》(Cell)杂志。国际同行认为,该成果对衰老和神经细胞退化性疾病的研究有重要意义。
刘北东等人根据观察到的蛋白聚合体在细胞中形成的稳定纤维结构与肌动蛋白骨架结构位置重合、敲除细胞极化机制导致细胞蛋白聚合体的隔离缺失等现象,进一步证实了蛋白聚合体的隔离是肌动蛋白和极化机制所参与的主动过程。此发现纠正了以往认为该隔离机制是一个完全被动过程的看法。
刘北东一直致力于微生物技术研究。2010年,其论文《细胞极化体是受损蛋白聚合体在细胞内隔离和逆向传输的重要因子》在《细胞》杂志发表,被认为在酵母菌细胞内发现了一个崭新的生物过程,该过程对生物体的衰老和后代的衰老时钟的重新设定起重要作用;国际权威学者还在同期杂志撰文予以高度评价。(生物谷Bioon.com)
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doi:10.1016/j.cell.2011.11.018
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Segregation of Protein Aggregates Involves Actin and the Polarity Machinery
Beidong Liu, Lisa Larsson, Vanessa Franssens, Xinxin Hao, Sandra Malmgren Hill, Veronica Andersson, Daniel Höglund, Jia Song, Xiaoxue Yang, David Öling et al.
Cells of yeast to mammals have evolved the means of spatial quality control (SQC), which includes the transport of protein aggregates on microtubules into a structure called the aggresome (Kopito, 2000,Wang et al., 2009) and a factor-dependent compartmentalization of aggregates into juxtanuclear sites (JUNQ) and perivacuolar inclusions (IPOD) (Kaganovich et al., 2008). SQC also encompasses an actin cytoskeleton-, polarisome-, and Hsp104-dependent segregation of damaged proteins during yeast cytokinesis (Aguilaniu et al., 2003,Erjavec et al., 2007,Tessarz et al., 2009). In addition, some aggregates in yeast daughter cells were observed to move (retrograde) into the mother cell after a transient heat stress (Liu et al., 2010). In this issue of Cell, Zhou et al., 2011 now extend this analysis and, with the aid of theoretical simulations, suggest that motility of protein aggregates is characterized by random and slow diffusion, completely devoid of directional bias. Further, it is argued that aggregate asymmetry is established in a purely passive and random manner and that no active, factor-dependent (e.g., polarisome) mechanism is involved in conferring SQC. This model contrasts that of Tessarz et al., 2009 and Liu et al., 2010, which both interpret the failure of mutants with defects in polarisome and Hsp104 functions to establish damage asymmetry indicative of damage retention being a factor-dependent process.
When considering the different views on the establishment of damage asymmetry, it should be pointed out that measurements aimed at determining the frequency of aggregate movement between mother and daughter should only include budding events in which such transfer is physically possible. This is the case during the S to early G2 phase, when the polarisome is localized at the bud tip and actin cables extend from the bud into the mother compartment. When these phases are considered, our data show that there is a bias toward retrograde movement of aggregates from daughter to mother. In 393 budding events analyzed (between 56 and 84 such events were analyzed in the Zhou et al. study), we found that 15.5% showed cross-compartment movements (Figure 1A), and among these, retrograde movement from bud to mother (66.5%) is significantly more frequent than anterograde movement (25.4%; p = 0.03) and movement in both directions (8.1%; p = 0.007) (Figure 1B). Figure S1 in the Supplemental Information available online shows two budding events with simultaneously retrograde movement of aggregates (Movie S1. An Uncropped Full-Field Movie Showing Several Budding Events with Retrograde Movement is an uncropped full-field movie showing several retrograde movements).