SPINDLY 与赤霉素的信号转导

SPINDLY(SPY)作为一负调节子参与GA的信号转导,34肽重复结构(TPR)与C-端区域对其正常功能都十分重要。SPY基因在植物中呈组成型表达,其蛋白主要出现在细胞核部位。SPY蛋白与动物中的氧连N-乙酰葡萄糖胺转移酶(OGT)具有广泛的同源性,两者可能有着类似的作用机制。本文主要介绍GA突变体、SPY基因、SPY蛋白及其在大麦中的同源物HvSPY的结构与功能相关方面的一些研究进展。     

VEGF and Notch Signaling

Tubular sprouting in angiogenesis relies on division of labour between the endothelial tip cell, leading and guiding the sprout and their neighbouring stalk cells, which divide and form the vascular lumen. We previously learned how the graded extracellular distribution of heparin-binding Vascular Endothelial Growth Factor (VEGF)-A orchestrates and balances tip and stalk cell behaviour. Recent data now provided insight into the regulation of tip cell numbers, illustrating how Delta-like (Dll)4 – Notch signalling functions to limit the explorative tip cell behaviour induced by VEGF-A. These data also provided a first answer to the question why not all endothelial cells stimulated by VEGF-A turn into tip cells. Here we review this new model and discuss how VEGF-A and Dll4/Notch signalling may interact dynamically at cellular level to control vascular patterning.     

SPINDLY与赤霉素的信号转导

SPINDLY(SPY)作为一负调节子参与GA的信号转导,34肽重复结构(TPR)与C-端区域对其正常功能都十分重要.SPy基因在植物中呈组成型表达,其蛋白主要出现在细胞核部位.SPY蛋白与动物中的氧连N-乙酰葡萄糖胺转移酶(OGT)具有广泛的同源性,两者可能有着类似的作用机制.本文主要介绍GA突变体、SPy基因、SPY蛋白及其在大麦中的同源物HvSPY的结构与功能相关方面的一些研究进展.     

Signaling unmasked

Autophagy contributes to the removal of harmful cellular refuse, whereas catalase plays an important protective role by detoxifying reactive oxygen species. We recently found that autophagy and catalase are also required for promoting programmed cell death induced during plant immune responses. Here we discuss the difficulties in identifying cell death effectors, which are also required to maintain cellular homeostasis, and how their prodeath roles were unmasked using an unbiased forward genetics approach.     

Hedgehog信号通路与脂肪形成

Hedgehog(Hh)信号通路是从果蝇到人类都非常保守的信号通路,在脊椎动物和非脊椎动物胚胎期多种组织器官的发育中发挥着重要作用。Hh信号通路的异常会导致疾病(先天性缺陷和癌症)的发生。近年的研究发现,Hh信号通路在脂肪生长发育中发挥重要作用,激活Hh信号通路能特异性地抑制白色脂肪组织细胞的分化,而对棕色脂肪组织细胞分化没有作用。该文综述了Hh信号通路在脂肪细胞分化中的作用及其分子机制,并对今后的研究和应用作了展望。     

Integrins: Structure and Signaling

Integrins are cell surface transmembrane glycoproteins that function as adhesion receptors in cell-extracellular matrix interactions and link the matrix proteins to the cytoskeleton. The family of human integrins comprises 24 members, each of which is a heterodimer consisting of 1 of 18 alpha- and 1 of 8 beta-subunits. Integrins play an important role in the cytoskeleton organization and in transduction of intracellular signals, regulating various processes such as proliferation, differentiation, apoptosis, and cell migration. This review summarizes current views on the structure of integrins, integrin associated proteins, and biochemical mechanisms underlying their signaling functions.     

mTOR信号通路与调节

哺乳动物雷帕霉素靶蛋白mTOR是一种非典型丝氨酸／苏氨酸蛋白激酶,可整合细胞外信号,磷酸化下游靶蛋白核糖体p70S6激酶,如S6K1及4E—BP1,影响转录与翻译,从而参与调控细胞生长、增殖等过程。近年来研究发现,调控mTOR通路可以干预某些疾病的病理过程。mTOR研究的新发现,可望为今后相关疾病的治疗提供新的靶点。     

Endocytosis and Signaling during Development

The development of multicellular organisms relies on an intricate choreography of intercellular communication events that pattern the embryo and coordinate the formation of tissues and organs. It is therefore not surprising that developmental biology, especially using genetic model organisms, has contributed significantly to the discovery and functional dissection of the associated signal-transduction cascades. At the same time, biophysical, biochemical, and cell biological approaches have provided us with insights into the underlying cell biological machinery. Here we focus on how endocytic trafficking of signaling components (e.g., ligands or receptors) controls the generation, propagation, modulation, reception, and interpretation of developmental signals. A comprehensive enumeration of the links between endocytosis and signal transduction would exceed the limits of this review. We will instead use examples from different developmental pathways to conceptually illustrate the various functions provided by endocytic processes during key steps of intercellular signaling.The evolution of multicellular life introduced a division of labor between specialized cells, which strongly increased demand for intercellular communication both during development and homeostasis of the adult organism (Kaiser 2001). At the genomic level this is reflected by a dramatic expansion of the surface receptor signalome in all metazoan lineages (Ben-Shlomo et al. 2003). However, the idea that intercellular communication drives the organization and patterning of the embryo precedes the identification of the responsible molecules. Induction (i.e., the ability of one group of cells within a developing organism to influence the cell-fate choices), morphogenesis, and differentiation of other cell populations, was firmly established by the experiments of Spemann and Mangold (1924) and has become one of the most important concepts of developmental biology. The related concept of the morphogen, whereby a cell can identify its position within a tissue by using the local levels of a secreted molecule forming a concentration gradient as a proxy for its distance from the source, was famously illustrated by the “French flag Model” by Wolpert (1969).Since then, examples of developmental patterning events following these two paradigms have been identified in all developmental model systems, ranging from worms and flies to amphibians, fish, and mice, and even humans. Surprisingly, despite the huge variety in the eventual outcome of metazoan embryonic development, it turned out that most individual patterning events are performed by a restricted set of signal-transduction pathways that are used repeatedly and in varying cellular contexts (Pires-daSilva and Sommer 2003; Perrimon et al. 2012).Because animal embryos differ in shape and size, closely related pathways must function over similarly varying spatial and temporal scales, potentially even at successive developmental stages within the same embryo. To understand how the limited, intercellular signaling repertoire is modulated to accommodate the varying patterning needs arising within the different developmental contexts, it is necessary to study the signal-transduction machinery at the molecular level. In recent years, major progress has been made in understanding the mechanistic links between the protein trafficking machinery and the generation and interpretation of morphogenetic signals.Traditionally, endocytosis was seen as a means of removing activated receptors and their bound ligands from the surface of the signal-receiving cells, thereby terminating the signals. However, positive effects of endocytosis on signal transduction have recently been identified for many different pathways including, among others, receptor tyrosine kinases (RTKs), TGF-β, TNF-α, Toll-like receptor, Wnt, and Notch signal-transduction cascades (Miaczynska et al. 2004; Platta and Stenmark 2011). In many of these examples, endosomes act as platforms where the activated receptors can interact with specific downstream components of the signal-transduction machinery (Sadowski et al. 2009; Miaczynska and Bar-Sagi 2010). Trafficking of the receptors into and out of such endosomes may thus provide another tier for the regulation of the signaling output that allows temporal and spatial modulation of the signals independent of ligand presentation. In addition, the endocytic pathway has recently also become implicated in signaling events that precede the intracellular transduction of the signal. In this review, we therefore focus on how the endocytic machinery participates in the generation, propagation, reception, and interpretation of intercellular signals in the context of animal development.     

IL-17的信号传导及功能研究

白介素17(IL-17),辅助性T细胞T_H17分泌的特征性细胞因子,在抵抗胞外细菌、真菌感染的宿主防御以及各种自身免疫性疾病发病中起到了重要的作用。本文对T_B17细胞、IL-17的发现作了历史性回顾,并综述了IL-17受体介导的信号传导途径和生理功能的研究进展,为T_H17细胞、IL-17及其受体作为药物治疗的新靶点提供新思路。     

Signaling between nematodes and plants

After hatching in the soil, root-knot nematodes must locate and penetrate a root, migrate into the vascular cylinder, and establish a permanent feeding site. Presumably, these events are accompanied by extensive signaling between the nematode parasite and the host. Hence, much emphasis has been placed on identifying proteins that are secreted by the nematode during the migratory phase. Further progress in understanding the signaling events has been made recently by studying the host response. Striking parallels can be drawn between the nematode-plant interaction and plant symbioses with other microorganisms, and evidence is emerging to suggest that nematodes acquired components of their parasitic armory from those microbes.     

Signaling and myosin-binding protein C

Myosin-binding protein C (MyBP-C) is a thick filament protein consisting of 1274 amino acid residues (149 kDa) that was identified by Starr and Offer over 30 years ago as a contaminant present in a preparation of purified myosin. Since then, numerous studies have defined the muscle-specific isoforms, the structure, and the importance of the proteins in normal striated muscle structure and function. Underlying the critical role the protein plays, it is now apparent that mutations in the cardiac isoform (cMyBP-C) are responsible for a substantial proportion (30-40%) of genotyped cases of familial hypertrophic cardiomyopathy. Although generally accepted that MyBP-C can interact with all three filament systems within the sarcomere (the thick, thin, and titin filaments), the exact nature of these interactions and the functional consequences of modified binding remain obscure. In addition to these structural considerations, cMyBP-C can serve as a point of convergence for signaling processes in the cardiomyocyte via post-translational modifications mediated by kinases that phosphorylate residues in the cardiac-specific isoform sequence. Thus, cMyBP-C is a critical nodal point that has both important structural and signaling roles and whose modifications are known to cause significant human cardiac disease.