Emerging Roles and New Paradigms in Signaling Mechanisms of Plant Cryptochromes

Analogous to the opsin-based receptors in animals, plants contain a diverse and elaborate set of photoreceptors to perceive a much wider spectrum of light and adapt to varying light conditions. Cryptochromes (CRYs), the blue/UV-A light sensing receptors, represent one such class of photoreceptors found ubiquitously in plants. Although structurally similar to DNA photolyases which could repair UV-induced DNA damage, photoactivated CRYs, instead, initiate signal transduction pathways, which lead to gene expression changes and eventually more overt photomorphogenic responses. Apart from the well-established roles of CRYs in regulating seedling de-etiolation, flowering time, and circadian clock, recent reports have highlighted their roles in controlling other aspects of plant development as well. This review attempts to describe the novel/atypical roles of CRYs that have emerged in the past few years, and also present an account of the various signaling components involved in CRY signal transduction pathway.     

Patterning the embryo in higher plants: Emerging pathways and challenges

Embryogenesis, which establishes the basic body plan for the post-embryonic organs after stereotyped cell divisions, initiates the first step of the plant life cycle. Studies in the last two decades indicate that embryogenesis is a precisely controlled process, and any defect would result in abnormalities. Here we discuss the recent progresses, with a focus on the cellular pathways governing early embryogenesis in the model species Arabidopsis.     

Axon-Dependent Patterning and Maintenance of Somatosensory Dendritic Arbors

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BMP-1及BMP家族在背-腹轴图式形成中的作用

骨形态发生蛋白（bone morphogenetic proteins, BMPs）是一类在发育过程中起重要作用的分子。除BMP-1外,其他BMP分子均属于转化生长因子-β（transforming growth factor-β, TGF-β）/BMP超家族的发育信号分子。在胚胎发育过程中,这些信号分子通过形成浓度梯度对背—腹轴各向异性分化进行调控。它们借助细胞表面受体的识别进行信号传导,参与调控细胞分化、增殖等活动。而BMP-1则属于细胞外基质金属蛋白酶超家族中的Tolloid蛋白酶家族。BMP-1通过水解其他BMP的抑制物（如脊索发生素,Chordin）,达到促进其他BMP信号传导的目的。BMP-1、BMP和Chordin三者通过相互制约与相互促进等一系列作用,在背—腹沿线建立起稳定的BMP信号梯度。本文就BMP浓度梯度的形成及其稳态维持的机制进行回顾与总结。并在此基础上,对各个物种间BMP浓度梯度形成机制的异同,以及可能存在的协同进化进行比较、分析和讨论。     

Brain Pericytes: Emerging Concepts and Functional Roles in Brain Homeostasis

Brain pericytes are an important constituent of neurovascular unit. They encircle endothelial cells and contribute to the maturation and stabilization of the capillaries in the brain. Recent studies have revealed that brain pericytes play pivotal roles in a variety of brain functions, such as regulation of capillary flow, angiogenesis, blood brain barrier, immune responses, and hemostasis. In addition, brain pericytes are pluripotent and can differentiate into different lineages similar to mesenchymal stem cells. The brain pericytes are revisited as a key player to maintain brain function and repair brain damage.     

Cadherins in development and cancer

Proper embryonic development is guaranteed under conditions of regulated cell-cell and cell-matrix adhesion. The cells of an embryo have to be able to distinguish their neighbours as being alike or different. Cadherins, single-pass transmembrane, Ca(2+)-dependent adhesion molecules that mainly interact in a homophilic manner, are major contributors to cell-cell adhesion. Cadherins play pivotal roles in important morphogenetic and differentiation processes during development, and in maintaining tissue integrity and homeostasis. Changes in cadherin expression throughout development enable differentiation and the formation of various organs. In addition to these functions, cadherins have strong implications in tumourigenesis, since frequently tumour cells show deregulated cadherin expression and inappropriate switching among family members. In this review, I focus on E- and N-cadherin, giving an overview of their structure, cellular function, importance during development, role in cancer, and of the complexity of Ecadherin gene regulation.     

A Comparative Quantitative Assessment of Axonal and Dendritic mRNA Transport in Maturing Hippocampal Neurons

Translation of mRNA in axons and dendrites enables a rapid supply of proteins to specific sites of localization within the neuron. Distinct mRNA-containing cargoes, including granules and mitochondrial mRNA, are transported within neuronal projections. The distributions of these cargoes appear to change during neuronal development, but details on the dynamics of mRNA transport during these transitions remain to be elucidated. For this study, we have developed imaging and image processing methods to quantify several transport parameters that can define the dynamics of RNA transport and localization. Using these methods, we characterized the transport of mitochondrial and non-mitochondrial mRNA in differentiated axons and dendrites of cultured hippocampal neurons varying in developmental maturity. Our results suggest differences in the transport profiles of mitochondrial and non-mitochondrial mRNA, and differences in transport parameters at different time points, and between axons and dendrites. Furthermore, within the non-mitochondrial mRNA pool, we observed two distinct populations that differed in their fluorescence intensity and velocity. The net axonal velocity of the brighter pool was highest at day 7 (0.002±0.001 µm/s, mean ± SEM), raising the possibility of a presynaptic requirement for mRNA during early stages of synapse formation. In contrast, the net dendritic velocity of the brighter pool increased steadily as neurons matured, with a significant difference between day 12 (0.0013±0.0006 µm/s ) and day 4 (−0.003±0.001 µm/s) suggesting a postsynaptic role for mRNAs in more mature neurons. The dim population showed similar trends, though velocities were two orders of magnitude higher than of the bright particles. This study provides a baseline for further studies on mRNA transport, and has important implications for the regulation of neuronal plasticity during neuronal development and in response to neuronal injury.     

Aspergillus nidulans Protein O-Mannosyltransferases Play Roles in Cell Wall Integrity and Developmental Patterning

Protein O-mannosyltransferases (Pmts) initiate O-mannosyl glycan biosynthesis from Ser and Thr residues of target proteins. Fungal Pmts are divided into three subfamilies, Pmt1, -2, and -4. Aspergillus nidulans possesses a single representative of each Pmt subfamily, pmtA (subfamily 2), pmtB (subfamily 1), and pmtC (subfamily 4). In this work, we show that single Δpmt mutants are viable and have unique phenotypes and that the ΔpmtA ΔpmtB double mutant is the only viable double mutant. This makes A. nidulans the first fungus in which all members of individual Pmt subfamilies can be deleted without loss of viability. At elevated temperatures, all A. nidulans Δpmt mutants show cell wall-associated defects and increased sensitivity to cell wall-perturbing agents. The Δpmt mutants also show defects in developmental patterning. Germ tube emergence is early in ΔpmtA and more frequent in ΔpmtC mutants than in the wild type. In ΔpmtB mutants, intrahyphal hyphae develop. All Δpmt mutants show distinct conidiophore defects. The ΔpmtA strain has swollen vesicles and conidiogenous cells, the ΔpmtB strain has swollen conidiophore stalks, and the ΔpmtC strain has dramatically elongated conidiophore stalks. We also show that AN5660, an ortholog of Saccharomyces cerevisiae Wsc1p, is modified by PmtA and PmtC. The Δpmt phenotypes at elevated temperatures, increased sensitivity to cell wall-perturbing agents and restoration to wild-type growth with osmoticum suggest that A. nidulans Pmts modify proteins in the cell wall integrity pathway. The altered developmental patterns in Δpmt mutants suggest that A. nidulans Pmts modify proteins that serve as spatial cues.Filamentous fungi use highly polar growth to explore their environments. Except for a brief period of isotropic expansion just after spores break dormancy, filamentous fungi add new cell wall material exclusively at the tips of tubular hyphal cells. Such polar growth involves a high degree of coordination between signals from the environment and the secretory apparatus. In fungi, O mannosylation of specific target proteins has been shown to be important for sensing environmental stress, stabilizing the cell wall, and proper development (18, 28). The assembly of protein linked O-mannosyl glycans in the endoplasmic reticulum lumen is catalyzed by protein O-mannosyltransferases (Pmts), which transfer a single mannosyl residue to the hydroxyl group of serine or threonine residues to form an α-d-mannosyl linkage (30). The addition of further carbohydrate residues to the first O-linked mannose occurs in the Golgi apparatus and involves a range of enzymes (35). Modification by Pmts seems to be specific to proteins that are synthesized and sorted in the secretory pathway; however, the only motif so far identified is that Ser/Ter-rich membrane-bound proteins are O mannosylated by Pmt4 in Saccharomyces cerevisiae (15). This lack of a clear motif makes identification of Pmt targets by computational methods challenging. All of the fungal Pmt-modified proteins identified so far are localized to the cell membrane or cell wall or are secreted. At least 23 target proteins have been described in yeasts (15). Only three Pmt target proteins have been described in filamentous fungi (12, 23, 37).Pmts have been found in both prokaryotes and eukaryotes (33), but not in plants (8). The lengths and compositions of O-mannosyl glycans are different among species. In fungi, O-glycosyl chains range from 2 to 7 residues. In S. cerevisiae, the mannosyl chain can be modified by mannosyl phosphate (6). In Schizosaccharomyces pombe, the O-linked glycan is capped with 1 or 2 galactose residues (6). In the filamentous fungi so far examined, O-glycans are linear and branched, with 3 to 5 monosaccharide residues (4).In fungi, the Pmts are classified into the Pmt1, Pmt2, and Pmt4 subfamilies, with each species having three to seven members. S. cerevisiae and Candida albicans Pmts are the most redundant, with subfamilies 1 and 2 containing two or three members (7, 26). S. pombe and many filamentous fungi, including Aspergillus nidulans, have one representative from each subfamily. In S. cerevisiae, the enzymatic activity of Pmts requires interaction among members of the Pmt1 and Pmt2 subfamilies, while Pmt4 forms homomeric complexes (8). Heteromeric complexes between Pmt1 and Pmt2 subfamily members have also been reported in S. pombe (34).O mannosylation appears to be required for the stability, localization, and function of target proteins (18, 28, 32), and in vivo consequences of Pmt loss range from limited to lethal. In S. cerevisiae, O mannosylation is essential for cell integrity and cell wall rigidity (7). In C. albicans and Cryptococcus neoformans, Pmt mutation affects morphogenesis and virulence (24, 26, 27). In S. cerevisiae, strains with single Pmt subfamily representatives deleted are viable; however, deletion of subfamily 2 representatives is lethal in S. pombe and C. albicans (7, 34). In filamentous fungi, deletion of individual Pmts has been reported. Deletions of Trichoderma reesei pmtI, Aspergillus fumigatus pmt1, A. nidulans pmtA, and Aspergillus awamori pmtA were not lethal but affected growth and development (10, 22, 23, 37).In previous work, we identified the swoA mutant from a collection of temperature-sensitive polarity mutants and showed that the swoA allele encoded a Pmt2 subfamily member (PmtA) (21, 29). In this study, we use Δpmt strains to show that each of the three Pmts in A. nidulans (pmtA, pmtB, and pmtC) is nonessential but that all play distinct roles in cell wall integrity and developmental patterning. We also demonstrate that PmtA and PmtC modify an ortholog of S. cerevisiae Wsc1, a known Pmt target. Because of redundancy, all Pmt1 and Pmt2 subfamily members have not been deleted in S. cerevisiae. Because of lethality, the effects of loss of the Pmt2 subfamily cannot be addressed in S. pombe or C. albicans. This makes A. nidulans the first fungus in which the phenotypes of deleted strains for each Pmt subfamily have been reported.