植物肽类信号分子

近年来研究表明植物中也存在着肽类信号分子,类似于动物的肽激素。目前可分成三类：即EN-OD40、植物硫动蛋白（phytosulfokine）和系统素。ENOD40影响着细胞分裂,可能是参与控制了细胞对生长素的反应所致。植物硫动蛋白最初从芦笋叶肉细胞培养中分离,是一种减数分裂诱导因子,为细胞增殖必需,但具体机制还不清楚。系统素的研究较为深入,巳提出了它所激发的植物伤诱信号传导过程和模型。     

The Hippo–YAP pathway regulates the proliferation of alveolar epithelial progenitors after acute lung injury

Regeneration of pulmonary epithelial cells plays an important role in the recovery of acute lung injury (ALI), which is defined by pulmonary epithelial cell death. However, the mechanism of the regenerative capacity of alveolar epithelial cells is unknown. Using a lung injury mouse model induced by hemorrhagic shock and lipopolysaccharide, a protein mass spectrometry‐based high‐throughput screening and linage tracing technology to mark alveolar epithelial type 2 cells (AEC2s), we analyzed the mechanism of alveolar epithelial cells proliferation. We demonstrated that the expression of Hippo‐yes‐associated protein 1 (YAP1) key proteins were highly consistent with the regularity of the proliferation of alveolar epithelial type 2 cells after ALI. Furthermore, the results showed that YAP1+ cells in lung tissue after ALI were mainly Sftpc lineage‐labeled AEC2s. An in vitro proliferation assay of AEC2s demonstrated that AEC2 proliferation was significantly inhibited by both YAP1 small interfering RNA and Hippo inhibitor. These findings revealed that YAP functioned as a key regulator to promote AEC2s proliferation, with the Hippo signaling pathway playing a pivotal role in this process.     

TCR介导“inside-out”信号通路调控整合素的活化

整合素（integrin）是一类重要的跨膜黏附分子,在T细胞定向迁移到淋巴器官、感染或炎症部位以及T细胞与抗原呈递细胞（antigen presenting cell,APC）之间相互作用等过程中起重要作用。T细胞受到抗原或趋化因子等的刺激后,启动细胞内大量的信号传导分子,并形成＂inside-out＂信号通路,导致整合素构像的改变（conformation change）或促进整合素在细胞表面的聚集（integrinclustering）,最终增强整合素的affinity或avidity,促进其与配体结合的能力,提高淋巴细胞间的黏附。近年来的研究已经鉴定出调控整合素活化的多个关键的信号分子及其形成的信号转导复合体。该文主要阐述T细胞受到抗原刺激后,由T细胞受体（T cell receptor,TCR）介导的＂inside-out＂信号通路中关键的信号分子如ADAP、SKAP-55、RapL、Rap1、Talin和Kindlins等如何与上下游信号分子协同作用,调控整合素LFA-1活化的分子机制。     

Ligand Perception,Activation, and Early Signaling of Plant Steroid Receptor Brassinosteroid Insensitive

Leucine-rich repeat receptor-like kinases （LRR-RLKs） belong to a large group of cell surface proteins involved in many aspects of plant development and environmental responses in both monocots and dicots. Brassinosteroid insensitive 1 （BRI1）, a member of the LRR X subfamily, was first identified through several forward genetic screenings for mutants insensitive to brassinosteroids （BRs）, which are a class of plant-specific steroid hormones. Since its identification, BRI1 and its homologs had been proved as receptors perceiving BRs and initiating BR signaling. The co-receptor BRIl-associated kinase 1 and its homologs, and other BRI1 interacting proteins such as its inhibitor BRI1 kinase inhibitor I （BKI1） were identified by genetic andbiochemical approaches. The detailed mechanisms of BR perception by BRI1 and the activation of BRI1 receptor complex have also been elucidated. Moreover, several mechanisms for termination of the activated BRI1 signaling were also discovered. In this review, we will focus on the recent advances on the mechanism of BRI1 phosphorylation and activation, the regulation of its receptor complex, the structure basis of BRI1 ectodomain and BR recognition, its direct substrates, and the termination of the activated BRI1 receptor complex.     

胰岛素信号通路相关因子在2型糖尿病合并骨质疏松大鼠肝组织的表达

通过高糖高脂饲料联合小剂量链脲佐菌素和去卵巢手术制备2型糖尿病合并骨质疏松大鼠模型,探讨2型糖尿病合并骨质疏松大鼠肝组织胰岛素信号通路相关因子的表达及意义。结果表明:随着时间延长,2型糖尿病合并骨质疏松组(DOVX组)肝组织IGF-1、IRS-1较其他组mRNA及蛋白表达减少,单纯去卵巢组(NOVX组)IGF-1、IRS-1 mRNA及蛋白表达较假手术对照组(NS组)降低;糖尿病组(DS组)IRS-2较NS组mRNA及蛋白表达下降,但NOVX组与NS组IRS-2 mRNA及蛋白表达比较无明显差别。以上结果表明,2型糖尿病合并骨质疏松的发生可能与肝脏胰岛素信号通路受抑制有关。     

Wnt signaling regulates experience-dependent synaptic plasticity in the adult nervous system

Comment on: Jensen M, et al. Cell 2012; 149:173-87.     

In vivo administration of 1,25-dihydroxyvitamin D3 suppresses the expression of RANKL mRNA in bone of thyroparathyroidectomized rats constantly infused with PTH

It is known that pharmacological or toxic doses of vitamin D induce bone resorption both in vivo and in vitro, whereas physiological doses of the vitamin have a protective effect on bone in vivo. To investigate the discrepancies of the dose-dependent effect of vitamin D on bone resorption, we examined the in vivo effect of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] on the expression of the receptor activator of nuclear factor-kappaB (NF-kappaB) ligand (RANKL) and osteoprotegerin (OPG) mRNAs in bone of thyroparathyroidectomized (TPTX) rats infused with or without parathyroid hormone (PTH). Continuous infusion of 50 ng/h of PTH greatly increased the expression of RANKL mRNA in bone of TPTX rats. Expression of OPG mRNA was not altered by PTH infusion. When graded doses of 1,25(OH)(2)D(3) was daily administered orally for 14 days to normocalcemic TPTX rats constantly infused with PTH, 0.01 and 0.1 microg/kg of 1,25(OH)(2)D(3) inhibited the PTH-induced RANKL mRNA expression, but 0.5 microg/kg of the vitamin did not inhibit it. Regulator of G protein signaling-2 (RGS-2) gene expression was suppressed by 1,25(OH)(2)D(3) dose-dependently, but PTH/PTHrP receptor mRNA expression was not altered. Bone morphometric analyses revealed that 1,25(OH)(2)D(3) suppressed PTH-induced osteoclast number in vivo. These results suggest that pharmacological or toxic doses of 1,25(OH)(2)D(3) stimulate bone resorption by inducing RANKL, but a certain range of physiological doses of the vitamin inhibit PTH-induced bone resorption, the latter mechanism appeared to be mediated, at least in part, by the suppression of the PTH/PTHrP receptor-mediated signaling.     

Post-translational modifications in MeHg-induced neurotoxicity

Mercury (Hg) exposure remains a major public health concern due to its widespread distribution in the environment. Organic mercurials, such as MeHg, have been extensively investigated especially because of their congenital effects. In this context, studies on the molecular mechanism of MeHg-induced neurotoxicity are pivotal to the understanding of its toxic effects and the development of preventive measures. Post-translational modifications (PTMs) of proteins, such as phosphorylation, ubiquitination, and acetylation are essential for the proper function of proteins and play important roles in the regulation of cellular homeostasis. The rapid and transient nature of many PTMs allows efficient signal transduction in response to stress. This review summarizes the current knowledge of PTMs in MeHg-induced neurotoxicity, including the most commonly PTMs, as well as PTMs induced by oxidative stress and PTMs of antioxidant proteins. Though PTMs represent an important molecular mechanism for maintaining cellular homeostasis and are involved in the neurotoxic effects of MeHg, we are far from understanding the complete picture on their role, and further research is warranted to increase our knowledge of PTMs in MeHg-induced neurotoxicity.     

抗病毒天然免疫研究

病毒是一种极具感染性和传染性的病原微生物．当病毒感染机体以后,机体会通过激活免疫系统来进行防御．高等哺乳动物的免疫系统分为两大类：适应性免疫系统和天然免疫系统．适应性免疫系统主要通过T淋巴细胞和B淋巴细胞特异性地识别入侵的病毒并将其清除．而天然免疫系统主要通过模式识别受体识别病毒的入侵,进而产生一系列的细胞因子抵抗病毒的入侵．其中,天然免疫系统作为抵御病毒入侵的第一道防线和激活后续适应性免疫的先决条件在整个抗病毒免疫反应中发挥着十分重要的作用．     

Slit/Robo信号在血管新生中的功能研究

分泌型糖蛋白Slit及其受体Roundabout(Robo)最初是作为一类重要的发育中神经元轴突导向分子而被发现的。目前为止对Slit/Robo信号对神经系统发育过程中轴突吸引或排斥的导向功能研究比较多,而对在发育中生长方式与其非常相似的血管发生过程中研究比较少。现有研究提示两者在发育过程中可能存在共同的信号调控机制,是Slit/Robo信号通路在血管新生中充当着重要的角色。该文就Slit/Robo信号对血管内皮细胞迁移的调节、对血管新生的作用及其可能介导的信号通路进行综述,以期进一步推动Slit/Robo信号通路在血管发生中的研究。