Proteomic analysis of blastema formation in regenerating axolotl limbs.
Proteomic analysis of blastema formation in regenerating axolotl limbs.
复制标题
再生Axolotl肢体中胚泡形成的蛋白质组学分析。
DOI：
10.1186/1741-7007-7-83
复制
发表时间：
2009-11-30
期刊：
影响因子：
5.4
通讯作者：
Stocum DL
中科院分区：
文献类型：
--
作者：
Rao N;Jhamb D;Milner DJ;Li B;Song F;Wang M;Voss SR;Palakal M;King MW;Saranjami B;Nye HL;Cameron JA;Stocum DL
截肢后，有尾目蝾螈的肢体重新编程体细胞，形成一个芽基，自组织成缺失的肢体部分，以恢复肢体的结构和功能。为了帮助理解芽基形成的分子基础，我们使用定量无标记液相色谱-质谱/质谱（LC-MS/MS）为基础的方法来分析发生在截肢后1，4和7天（dpa）通过中部的美西螈后肢胫骨/腓骨的蛋白质组的变化。我们鉴定了309种相对于对照组（0 dpa）具有显著倍数变化的独特蛋白质，代表10种生物过程类别：（1）信号传导，（2）Ca 2+结合和易位，（3）转录，（4）翻译，（5）细胞骨架，（6）细胞外基质（ECM），（7）代谢，（8）细胞保护，（9）降解和（10）细胞周期。总共有43种蛋白质表现出异常高的倍数变化。其中，亲嗜性病毒整合因子5（EVI 5），一种细胞周期相关的癌蛋白，防止细胞过早进入细胞周期的有丝分裂期，是特别感兴趣的，因为它的倍数变化是非常高的整个胚基形成。我们的数据与以前的研究一致，表明三磷酸肌醇和Ca 2+信号在启动ECM和细胞骨架重塑特征的组织溶解和细胞去分化中的重要性。此外，这些数据表明，芽基的形成需要几种机制来避免细胞凋亡，包括减少代谢，促凋亡和抗凋亡蛋白的差异调节，以及未折叠蛋白反应（UPR）的启动。由于芽基形成过程中几乎没有有丝分裂，我们提出高水平的EVI 5的功能是在细胞周期的G1/S/G2期阻止去分化细胞，直到它们在伤口表皮下积累并响应神经和表皮因子进入有丝分裂。我们的研究结果表明，定量蛋白质组学分析在理解复杂结构的再生的一般价值。
Following amputation, urodele salamander limbs reprogram somatic cells to form a blastema that self-organizes into the missing limb parts to restore the structure and function of the limb. To help understand the molecular basis of blastema formation, we used quantitative label-free liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS)-based methods to analyze changes in the proteome that occurred 1, 4 and 7 days post amputation (dpa) through the mid-tibia/fibula of axolotl hind limbs. We identified 309 unique proteins with significant fold change relative to controls (0 dpa), representing 10 biological process categories: (1) signaling, (2) Ca2+ binding and translocation, (3) transcription, (4) translation, (5) cytoskeleton, (6) extracellular matrix (ECM), (7) metabolism, (8) cell protection, (9) degradation, and (10) cell cycle. In all, 43 proteins exhibited exceptionally high fold changes. Of these, the ecotropic viral integrative factor 5 (EVI5), a cell cycle-related oncoprotein that prevents cells from entering the mitotic phase of the cell cycle prematurely, was of special interest because its fold change was exceptionally high throughout blastema formation. Our data were consistent with previous studies indicating the importance of inositol triphosphate and Ca2+ signaling in initiating the ECM and cytoskeletal remodeling characteristic of histolysis and cell dedifferentiation. In addition, the data suggested that blastema formation requires several mechanisms to avoid apoptosis, including reduced metabolism, differential regulation of proapoptotic and antiapoptotic proteins, and initiation of an unfolded protein response (UPR). Since there is virtually no mitosis during blastema formation, we propose that high levels of EVI5 function to arrest dedifferentiated cells somewhere in the G1/S/G2 phases of the cell cycle until they have accumulated under the wound epidermis and enter mitosis in response to neural and epidermal factors. Our findings indicate the general value of quantitative proteomic analysis in understanding the regeneration of complex structures.
登录
查看更多内容
影响因子：
64.8
作者：
CAMERON, JA;HILGERS, AR;HINTERBERGER, TJ
通讯作者：
HINTERBERGER, TJ
影响因子：
2.9
作者：
Caldwell, Robert L.;Opalenik, Susan R.;Nanney, Lillian B.
通讯作者：
Nanney, Lillian B.
DOI：
10.1098/rspb.1995.0024
发表时间：
1995-02-22
影响因子：
4.7
作者：
CREWS, L;GATES, PB;GANN, AAF
通讯作者：
GANN, AAF
DOI：
10.1196/annals.1402.047
发表时间：
2007-01-01
期刊：
SKELETAL BIOLOGY AND MEDICINE, PT A
影响因子：
--
作者：
Bergenstock, Marika K.;Partridge, Nicola C.
通讯作者：
Partridge, Nicola C.
影响因子：
4
作者：
Abraham, ST;Shaw, C
通讯作者：
Shaw, C