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- Larhammar, Dan, et al.
(författare)
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Peptide hormone and receptor evolution
- 2007
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Ingår i: General and Comparative Endocrinology. - : Elsevier BV. - 0016-6480 .- 1095-6840. ; 153:1-3, s. 147-
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Tidskriftsartikel (refereegranskat)abstract
- An important and fascinating theme that unifies both invertebrate and vertebrate endocrinologists is that of the evolution of peptide precursor and receptor genes. Peptide signalling plays a crucial role in processes that control decisive physiological events in organisms as divergent as yeast and mammals. The majority of small neuronal/endocrine peptides exert their functions via an interaction with heptahelical membrane receptors belonging to the G protein-coupled receptor superfamily, a large and diverse signal transducing protein category which has very ancient evolutionary roots. Most of the larger peptides and growth factors function via other well-conserved receptor classes that contain only a single transmembrane segment. The symposium on peptide hormone and receptor evolution brought together scientists studying peptide–receptor evolution in widely divergent metazoans. Two State-of-the-Art lectures gave overviews of current knowledge of peptide and receptor gene evolution. The sequencing and annotation of entire animal genomes constitutes a very exciting development that have already revolutionized the general views on metazoan macroevolution. The resulting burst of molecular data represents an impressive boost of novel opportunities for comparative and functional genomics research. Several vertebrate peptide and receptor families were described by Dan Larhammar to have multiplied in the 1–2 basal vertebrate tetraploidizations and in a third tetraploidization in ray-finned fishes before the radiation of teleosts. Families proposed to have multiplied in these events include NPY, tachykinins, opioid peptides, as well as the receptors for these three peptide families. The dynamics of coevolutionary change were discussed by Jozef Vanden Broeck based on several examples of peptide–receptor partners that show conservation across the protostomian–deuterostomian barrier. These examples include peptides belonging to the NPY, tachykinin, glycoprotein hormone and insulin-related peptide families, and their respective receptors. Additional examples of coevolution between peptides and their corresponding receptors in insects (the mosquito Aedes aegypti) and chelicerates (the tick Boophilus microplus) were presented by Ron Nachman. His detailed analysis of peptide receptor pharmacology has led to the production and selection of peptidomimetic compounds which specifically activate a particular receptor, while showing enhanced resistance against peptidases. This type of work may ultimately lead to the creation of novel, environmentally safe pest agents for insect management. In two other presentations, the evolution of two quite complex vertebrate peptide receptor systems were discussed. The five divergent and presumably ancient melanocortin receptors found in mammals have only three orthologues in the two sharks investigated so far (Angela Baron). Both the ά-MSH receptor MC1 and the ACTH receptor MC2 still remain to be identified or may have been lost or become widely divergent. The evolution of the large VIP/PACAP/secretin family (Florbela Vieira) involves duplicate PACAP genes in teleost fishes, whereas only a single VIP gene seems to exist. The PACAP gene and its chromosomal environment is more strongly conserved than the VIP gene. Invertebrates only have a single member most closely resembling PACAP. The concluding discussion largely revolved around the proposed tetraploidizations in early vertebrate evolution. While some hesitation still lingers, there is nevertheless no alternative explanation that can account better than the chromosome duplication (and tetraploidization) scenario for the extensive chromosome similarities and the high number of gene duplications that arose before gnathostomatous radiation. Additional gene duplications in early vertebrates were mentioned leading to the somatostatin 2-urotensin II gene pair and the somatostain 1-urotensin II-related peptide gene pair (Hervé Tostivint). Also the possible orthology relationships between peptides described in invertebrates, particularly insects, and vertebrates were discussed. Undoubtedly, definitive orthology relationships of neuropeptide precursor genes between protostomes and deuterostomes are often difficult to determine from sequence comparisons only, and will hopefully be aided by information on chromosome locations and gene neighbours.
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| 2. |
- Nässel, Dick R., et al.
(författare)
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Insulin/IGF signaling in Drosophila and other insects : factors that regulate production, release and post-release action of the insulin-like peptides
- 2016
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Ingår i: Cellular and Molecular Life Sciences (CMLS). - : Springer Science and Business Media LLC. - 1420-682X .- 1420-9071. ; 73:2, s. 271-290
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Forskningsöversikt (refereegranskat)abstract
- Insulin, insulin-like growth factors (IGFs) and insulin-like peptides (ILPs) are important regulators of metabolism, growth, reproduction and lifespan, and mechanisms of insulin/IGF signaling (IIS) have been well conserved over evolution. In insects, between one and 38 ILPs have been identified in each species. Relatively few insect species have been investigated in depth with respect to ILP functions, and therefore we focus mainly on the well-studied fruitfly Drosophila melanogaster. In Drosophila eight ILPs (DILP1-8), but only two receptors (dInR and Lgr3) are known. DILP2, 3 and 5 are produced by a set of neurosecretory cells (IPCs) in the brain and their biosynthesis and release are controlled by a number of mechanisms differing between larvae and adults. Adult IPCs display cell-autonomous sensing of circulating glucose, coupled to evolutionarily conserved mechanisms for DILP release. The glucose-mediated DILP secretion is modulated by neurotransmitters and neuropeptides, as well as by factors released from the intestine and adipocytes. Larval IPCs, however, are indirectly regulated by glucose-sensing endocrine cells producing adipokinetic hormone, or by circulating factors from the intestine and fat body. Furthermore, IIS is situated within a complex physiological regulatory network that also encompasses the lipophilic hormones, 20-hydroxyecdysone and juvenile hormone. After release from IPCs, the ILP action can be modulated by circulating proteins that act either as protective carriers (binding proteins), or competitive inhibitors. Some of these proteins appear to have additional functions that are independent of ILPs. Taken together, the signaling with multiple ILPs is under complex control, ensuring tightly regulated IIS in the organism.
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| 3. |
- Poels, Jeroen, et al.
(författare)
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Characterization and distribution of NKD, a receptor for Drosophila tachykinin-related peptide 6.
- 2009
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Ingår i: Peptides. - : Elsevier BV. - 0196-9781 .- 1873-5169. ; 30:3, s. 545-56
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Tidskriftsartikel (refereegranskat)abstract
- Neuropeptides related to vertebrate tachykinins have been identified in Drosophila and are referred to as drosotachykinins, or DTKs. Two Drosophila G protein-coupled receptors, designated NKD (neurokinin receptor from Drosophila; CG6515) and DTKR (Drosophila tachykinin receptor; CG7887), display sequence similarities to mammalian tachykinin receptors. Whereas DTKR was shown to be activated by DTKs [Birse RT, Johnson EC, Taghert PH, Nässel DR. Widely distributed Drosophila G-protein-coupled receptor (CG7887) is activated by endogenous tachykinin-related peptides. J Neurobiol 2006;66:33-46; Poels J, Verlinden H, Fichna J, Van Loy T, Franssens V, Studzian K, et al. Functional comparison of two evolutionary conserved insect neurokinin-like receptors. Peptides 2007;28:103-8] and was localized by immunocytochemistry in Drosophila central nervous system (CNS), agonist-dependent activation and distribution of NKD have not yet been investigated in depth. In the present study, we have challenged NKD-expressing mammalian and insect cells with a library of Drosophila neuropeptides and discovered DTK-6 as a specific agonist that can induce a calcium response in these cells. In addition, we have produced antisera to sequences from NKD protein to analyze receptor distribution. We found that NKD is less abundantly distributed in the central nervous system than DTKR, and only NKD was found in the intestine. In fact, the two receptors are distributed in mutually exclusive patterns in the CNS. The combined distribution of the receptors in brain neuropils corresponds well with the distribution of DTKs. Most interestingly, NKD appears to be activated only by DTK-6, known to possess an Ala-substitution in an otherwise conserved C-terminal core motif. Our findings suggest that NKD and DTKR provide substrates for two functionally and spatially separated peptide signaling systems.
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