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Renu Goel Krishna R Murthy Srinivas M Srikanth Sneha M Pinto Mitali Bhattacharjee Dhanashree S Kelkar Anil K Madugundu Gourav Dey Sujatha S Mohan Venkatarangaiah Krishna TS Keshava Prasad Shukti Chakravarti HC Harsha Akhilesh Pandey 《Clinical proteomics》2013,10(1):9
Background
The ciliary body is the circumferential muscular tissue located just behind the iris in the anterior chamber of the eye. It plays a pivotal role in the production of aqueous humor, maintenance of the lens zonules and accommodation by changing the shape of the crystalline lens. The ciliary body is the major target of drugs against glaucoma as its inhibition leads to a drop in intraocular pressure. A molecular study of the ciliary body could provide a better understanding about the pathophysiological processes that occur in glaucoma. Thus far, no large-scale proteomic investigation has been reported for the human ciliary body.Results
In this study, we have carried out an in-depth LC-MS/MS-based proteomic analysis of normal human ciliary body and have identified 2,815 proteins. We identified a number of proteins that were previously not described in the ciliary body including importin 5 (IPO5), atlastin-2 (ATL2), B-cell receptor associated protein 29 (BCAP29), basigin (BSG), calpain-1 (CAPN1), copine 6 (CPNE6), fibulin 1 (FBLN1) and galectin 1 (LGALS1). We compared the plasma proteome with the ciliary body proteome and found that the large majority of proteins in the ciliary body were also detectable in the plasma while 896 proteins were unique to the ciliary body. We also classified proteins using pathway enrichment analysis and found most of proteins associated with ubiquitin pathway, EIF2 signaling, glycolysis and gluconeogenesis.Conclusions
More than 95% of the identified proteins have not been previously described in the ciliary body proteome. This is the largest catalogue of proteins reported thus far in the ciliary body that should provide new insights into our understanding of the factors involved in maintaining the secretion of aqueous humor. The identification of these proteins will aid in understanding various eye diseases of the anterior segment such as glaucoma and presbyopia. 相似文献2.
Brooke R Snyder Pei-Hsun Cheng Jinjing Yang Shang-Hsun Yang Anderson HC Huang Anthony WS Chan 《BMC cell biology》2011,12(1):1-8
Background
Activation by extracellular ligands of G protein-coupled (GPCRs) and tyrosine kinase receptors (RTKs), results in the generation of second messengers that in turn control specific cell functions. Further, modulation/amplification or inhibition of the initial signalling events, depend on the recruitment onto the plasma membrane of soluble protein effectors. High throughput methodologies to monitor quantitatively second messenger production, have been developed over the last years and are largely used to screen chemical libraries for drug development. On the contrary, no such high throughput methods are yet available for the other aspect of GPCRs regulation, i.e. protein translocation to the plasma membrane, despite the enormous interest of this phenomenon for the modulation of receptor downstream functions. Indeed, to date, the experimental procedures available are either inadequate or complex and expensive.Results
Here we describe the development of a novel conceptual approach to the study of cytosolic proteins translocation to the inner surface of the plasma membrane. The basis of the technique consists in: i) generating chimeras between the protein of interests and the calcium (Ca2+)-sensitive, luminescent photo-protein, aequorin and ii) taking advantage of the large Ca2+ concentration [Ca2+] difference between bulk cytosolic and the sub-plasma membrane rim.Conclusion
This approach, that keeps unaffected the translocation properties of the signalling protein, can in principle be applied to any protein that, upon activation, moves from the cytosol to the plasma membrane. Thus, not only the modulation of GPCRs and RTKs can be investigated in this way, but that of all other proteins that can be recruited to the plasma membrane also independently of receptor activation. Moreover, its automated version, which can provide information about the kinetics and concentration-dependence of the process, is also applicable to high throughput screening of drugs affecting the translocation process. 相似文献3.
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Sexually selected traits that are costly are predicted to be more condition dependent than nonsexually selected traits. Assuming resource limitation, increased allocation to a sexually selected trait may also come at a cost to other fitness components. To test these predictions, we varied adult food ration to manipulate condition in the colour dimorphic bug, Phymata americana. We compared the degree of condition dependence in a sexually selected trait expressed in males to a nonsexually selected trait expressed in males and females. We also evaluated the effects of condition on longevity of both sexes. We found that the expression of these colour pattern traits was strongly influenced by both diet and age. As expected, the strength of condition dependence was much more pronounced in the sexually selected, male-limited trait but the nonsexual trait also exhibited significant condition dependence in both sexes. The sexually selected male trait also exhibited a higher coefficient of phenotypic variation than the nonsexually selected trait in males and females. Diet had contrasting effects on male and female longevity; increased food availability had positive effects on female lifespan but these effects were not detected in males, suggesting that males allocated limited resources preferentially to sexually selected traits. These results are consistent with the expectation that optimal allocation to various fitness components differs between the sexes. 相似文献
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Laura Kay Ilse S. Pienaar Ruwini Cooray Gary Black Meera Soundararajan 《Molecular neurobiology》2018,55(9):7352-7365
The Miro GTPases represent an unusual subgroup of the Ras superfamily and have recently emerged as important mediators of mitochondrial dynamics and for maintaining neuronal health. It is now well-established that these enzymes act as essential components of a Ca2+-sensitive motor complex, facilitating the transport of mitochondria along microtubules in several cell types, including dopaminergic neurons. The Miros appear to be critical for both anterograde and retrograde mitochondrial transport in axons and dendrites, both of which are considered essential for neuronal health. Furthermore, the Miros may be significantly involved in the development of several serious pathological processes, including the development of neurodegenerative and psychiatric disorders. In this review, we discuss the molecular structure and known mitochondrial functions of the Miro GTPases in humans and other organisms, in the context of neurodegenerative disease. Finally, we consider the potential human Miros hold as novel therapeutic targets for the treatment of such disease. 相似文献
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Ron A.-J Chen Grigory Ryzhakov Samantha Cooray Felix Randow Geoffrey L Smith 《PLoS pathogens》2008,4(2)
The IκB kinase (IKK) complex is a key regulator of signal transduction pathways leading to the induction of NF-κB-dependent gene expression and production of pro-inflammatory cytokines. It therefore represents a major target for the development of anti-inflammatory therapeutic drugs and may be targeted by pathogens seeking to diminish the host response to infection. Previously, the vaccinia virus (VACV) strain Western Reserve B14 protein was characterised as an intracellular virulence factor that alters the inflammatory response to infection by an unknown mechanism. Here we demonstrate that ectopic expression of B14 inhibited NF-κB activation in response to TNFα, IL-1β, poly(I:C), and PMA. In cells infected with VACV lacking gene B14R (vΔB14) there was a higher level of phosphorylated IκBα but a similar level of IκBα compared to cells infected with control viruses expressing B14, suggesting B14 affects IKK activity. Direct evidence for this was obtained by showing that B14 co-purified and co-precipitated with the endogenous IKK complex from human and mouse cells and inhibited IKK complex enzymatic activity. Notably, the interaction between B14 and the IKK complex required IKKβ but not IKKα, suggesting the interaction occurs via IKKβ. B14 inhibited NF-κB activation induced by overexpression of IKKα, IKKβ, and a constitutively active mutant of IKKα, S176/180E, but did not inhibit a comparable mutant of IKKβ, S177/181E. This suggested that phosphorylation of these serine residues in the activation loop of IKKβ is targeted by B14, and this was confirmed using Ab specific for phospho-IKKβ. 相似文献
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Yanwen Jiang David Redmond Kui Nie Ken W Eng Thomas Clozel Peter Martin Leonard HC Tan Ari M Melnick Wayne Tam Olivier Elemento 《Genome biology》2014,15(8)