Drosophila melanogaster is since decades the most important invertebrate model. With the publishing of the genome sequence, Drosophila also became a pioneer in (neuro)peptide research. Neuropeptides represent a major group of signaling molecules that outnumber all other types of neurotransmitters/modulators and hormones. By means of bioinformatics 119 (neuro)peptide precursor genes have been predicted from the Drosophila genome. Using the neuropeptidomics technology 46 neuropeptides derived from 19 of these precursors could be biochemically characterized. At the cellular level, neuropeptides usually exert their action by binding to membrane receptors, many of which belong to the family of G-protein coupled receptors or GPCRs. Such receptors are the major target for many contemporary drugs. In this chapter, we will describe the identification, localization and functional characterization of neuropeptide-receptor pairs in Drosophila melanogaster.
Introduction: Drosophila as a Model to Study Neuropeptide SignalingDrosophila has revolutionized biology more than any other organism. The entire genus contains about 1,500 species and is very diverse in appearance, behavior and breeding habitat. One species in particular, Drosophila melanogaster, has been heavily used in research in genetics and developmental biology. Also for neuropeptide research Drosophila is a very suitable model organism, especially since its genome has been nearly fully sequenced and is publicly accessible. 1 Neuropeptides form the largest class of signaling molecules in animals. They transmit and regulate bio-information in the circulatory as well as the neuronal system and exert their role mostly by acting on G-protein coupled receptors or GPCRs. As such, neuropeptides play critical roles in regulating most biological processes. Neuropeptides are diverse in structure, localization and function. Their only common feature is that they are all synthesized as peptide precursor proteins, also called preproproteins. Besides the neuropeptides themselves, also the receptors they act on are structurally diverse and the resulting signaling cascades are also highly varied, so there is a tremendous potential of different effects on living cells. Therefore, peptides are attractive for pharmaceutical and agro-industrial companies because they represent (lead) compounds that can be further exploited for diverse practical applications. Peptides as such cannot be used as therapeutics or as insecticides, because they are usually broken down before they reach their target. Therefore, small compounds called peptidomimetics that mimic or block the interaction of the peptide with its receptor are being developed. As more genomes become available, the findings in Drosophila can be readily expanded to other species, including those of economic interest.
Globally, colorectal cancer (CRC) is the third most common malignant neoplasm. However, highly sensitive, specific, noninvasive tests that allow CRC diagnosis at an early stage are still needed. As circulatory blood reflects the physiological status of an individual and/or the disease status for several disorders, efforts have been undertaken to identify candidate diagnostic CRC markers in plasma and serum. In this review, the challenges, bottlenecks and promising properties of mass spectrometry (MS)-based proteomics in blood are discussed. More specifically, important aspects in clinical design, sample retrieval, sample preparation, and MS analysis are presented. The recent developments in targeted MS approaches in plasma or serum are highlighted as well.
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