The Experts below are selected from a list of 131364 Experts worldwide ranked by ideXlab platform
Kentaro Hanada - One of the best experts on this subject based on the ideXlab platform.
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serine palmitoyltransferase a Key Enzyme of sphingolipid metabolism
Biochimica et Biophysica Acta, 2003Co-Authors: Kentaro HanadaAbstract:Abstract The first step in the biosynthesis of sphingolipids is the condensation of serine and palmitoyl CoA, a reaction catalyzed by serine palmitoyltransferase (SPT) to produce 3-ketodihydrosphingosine (KDS). This review focuses on recent advances in the biochemistry and molecular biology of SPT. SPT belongs to a family of pyridoxal 5′-phosphate (PLP)-dependent α-oxoamine synthases (POAS). Mammalian SPT is a heterodimer of 53-kDa LCB1 and 63-kDa LCB2 subunits, both of which are bound to the endoplasmic reticulum (ER) most likely with the type I topology, whereas other members of the POAS family are soluble homodimer Enzymes. LCB2 appears to be unstable unless it is associated with LCB1. Potent inhibitors of SPT structurally resemble an intermediate in a probable multistep reaction mechanism for SPT. Although SPT is a housekeeping Enzyme, its activity is regulated transcriptionally and post-transcriptionally, and its up-regulation is suggested to play a role in apoptosis induced by certain types of stress. Specific missense mutations in the human LCB1 gene cause hereditary sensory neuropathy type I, an autosomal dominantly inherited disease, and these mutations confer dominant-negative effects on SPT activity.
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serine palmitoyltransferase a Key Enzyme of sphingolipid metabolism
Biochimica et Biophysica Acta, 2003Co-Authors: Kentaro HanadaAbstract:The first step in the biosynthesis of sphingolipids is the condensation of serine and palmitoyl CoA, a reaction catalyzed by serine palmitoyltransferase (SPT) to produce 3-ketodihydrosphingosine (KDS). This review focuses on recent advances in the biochemistry and molecular biology of SPT. SPT belongs to a family of pyridoxal 5V (PLP)-dependent a-oxoamine synthases (POAS). Mammalian SPT is a heterodimer of 53-kDa LCB1 and 63-kDa LCB2 subunits, both of which are bound to the endoplasmic reticulum (ER) most likely with the type I topology, whereas other members of the POAS family are soluble homodimer Enzymes. LCB2 appears to be unstable unless it is associated with LCB1. Potent inhibitors of SPT structurally resemble an intermediate in a probable multistep reaction mechanism for SPT. Although SPT is a housekeeping Enzyme, its activity is regulated transcriptionally and post-transcriptionally, and its up-regulation is suggested to play a role in apoptosis induced by certain types of stress. Specific missense mutations in the human LCB1 gene cause hereditary sensory neuropathy type I, an autosomal dominantly inherited disease, and these mutations confer dominant-negative effects on SPT activity. D 2003 Elsevier Science B.V. All rights reserved.
Christian Wegener - One of the best experts on this subject based on the ideXlab platform.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
European Journal of Neuroscience, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:: Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well-characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila melanogaster lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours in Drosophila. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced viability and activity levels in adults. A phylogenomic analysis suggests that loss of CPE is not common to insects, but only occurred in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing and peptide-regulated behaviour in Drosophila. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. The persistent occurrence of CPD in insect genomes may point to important further CPD functions beyond neuropeptide processing which cannot be fulfilled by CPE.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
European Journal of Neuroscience, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well-characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila melanogaster lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours in Drosophila. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced viability and activity levels in adults. A phylogenomic analysis suggests that loss of CPE is not common to insects, but only occurred in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing and peptide-regulated behaviour in Drosophila. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. The persistent occurrence of CPD in insect genomes may point to important further CPD functions beyond neuropeptide processing which cannot be fulfilled by CPE.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
bioRxiv, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of Drosophila carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in adult starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced survival rate and activity levels. A phylogenomic analysis suggests that loss of CPE is not a common insect feature, but specifically occured in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing in Drosophila, and is required for proper peptide-regulated behaviour. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. Our results raise the question why Drosophila and other Diptera and Hymenoptera, unlike other insects, obviously have lost the gene for CPE but kept a gene encoding CPD.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
bioRxiv, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of Drosophila carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in adult starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced survival rate and activity levels. A phylogenomic analysis suggests that loss of CPE is not a common insect feature, but specifically occured in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing in Drosophila, and is required for proper peptide-regulated behaviour. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. Our results raise the question why Drosophila and other Diptera and Hymenoptera, unlike other insects, obviously have lost the gene for CPE but kept a gene encoding CPD.
Boris Gorke - One of the best experts on this subject based on the ideXlab platform.
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menage a trois post transcriptional control of the Key Enzyme for cell envelope synthesis by a base pairing small rna an rnase adaptor protein and a small rna mimic
RNA Biology, 2014Co-Authors: Yvonne Gopel, Muna A Khan, Boris GorkeAbstract:In Escherichia coli, small RNAs GlmY and GlmZ feedback control synthesis of glucosamine-6-phosphate (GlcN6P) synthase GlmS, a Key Enzyme required for synthesis of the cell envelope. Both small RNAs are highly similar, but only GlmZ is able to activate the glmS mRNA by base-pairing. Abundance of GlmZ is controlled at the level of decay by RNase adaptor protein RapZ. RapZ binds and targets GlmZ to degradation by RNase E via protein–protein interaction. GlmY activates glmS indirectly by protecting GlmZ from degradation. Upon GlcN6P depletion, GlmY accumulates and sequesters RapZ in an RNA mimicry mechanism, thus acting as an anti-adaptor. As a result, this regulatory circuit adjusts synthesis of GlmS to the level of its enzymatic product, thereby mediating GlcN6P homeostasis. The interplay of RNase adaptor proteins and anti-adaptors provides an elegant means how globally acting RNases can be re-programmed to cleave a specific transcript in response to a cognate stimulus.
Yasin Hamarat - One of the best experts on this subject based on the ideXlab platform.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
European Journal of Neuroscience, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:: Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well-characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila melanogaster lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours in Drosophila. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced viability and activity levels in adults. A phylogenomic analysis suggests that loss of CPE is not common to insects, but only occurred in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing and peptide-regulated behaviour in Drosophila. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. The persistent occurrence of CPD in insect genomes may point to important further CPD functions beyond neuropeptide processing which cannot be fulfilled by CPE.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
European Journal of Neuroscience, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well-characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila melanogaster lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours in Drosophila. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced viability and activity levels in adults. A phylogenomic analysis suggests that loss of CPE is not common to insects, but only occurred in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing and peptide-regulated behaviour in Drosophila. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. The persistent occurrence of CPD in insect genomes may point to important further CPD functions beyond neuropeptide processing which cannot be fulfilled by CPE.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
bioRxiv, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of Drosophila carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in adult starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced survival rate and activity levels. A phylogenomic analysis suggests that loss of CPE is not a common insect feature, but specifically occured in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing in Drosophila, and is required for proper peptide-regulated behaviour. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. Our results raise the question why Drosophila and other Diptera and Hymenoptera, unlike other insects, obviously have lost the gene for CPE but kept a gene encoding CPD.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
bioRxiv, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of Drosophila carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in adult starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced survival rate and activity levels. A phylogenomic analysis suggests that loss of CPE is not a common insect feature, but specifically occured in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing in Drosophila, and is required for proper peptide-regulated behaviour. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. Our results raise the question why Drosophila and other Diptera and Hymenoptera, unlike other insects, obviously have lost the gene for CPE but kept a gene encoding CPD.
Dennis Pauls - One of the best experts on this subject based on the ideXlab platform.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
European Journal of Neuroscience, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:: Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well-characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila melanogaster lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours in Drosophila. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced viability and activity levels in adults. A phylogenomic analysis suggests that loss of CPE is not common to insects, but only occurred in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing and peptide-regulated behaviour in Drosophila. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. The persistent occurrence of CPD in insect genomes may point to important further CPD functions beyond neuropeptide processing which cannot be fulfilled by CPE.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
European Journal of Neuroscience, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well-characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila melanogaster lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours in Drosophila. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced viability and activity levels in adults. A phylogenomic analysis suggests that loss of CPE is not common to insects, but only occurred in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing and peptide-regulated behaviour in Drosophila. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. The persistent occurrence of CPD in insect genomes may point to important further CPD functions beyond neuropeptide processing which cannot be fulfilled by CPE.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
bioRxiv, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of Drosophila carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in adult starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced survival rate and activity levels. A phylogenomic analysis suggests that loss of CPE is not a common insect feature, but specifically occured in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing in Drosophila, and is required for proper peptide-regulated behaviour. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. Our results raise the question why Drosophila and other Diptera and Hymenoptera, unlike other insects, obviously have lost the gene for CPE but kept a gene encoding CPD.
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drosophila carboxypeptidase d silver is a Key Enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate
bioRxiv, 2019Co-Authors: Dennis Pauls, Yasin Hamarat, Luisa Trufasu, Tim M Schendzielorz, Gertrud Gramlich, Jorg Kahnt, Jens T Vanselow, Andreas Schlosser, Christian WegenerAbstract:Neuropeptides are processed from larger preproproteins by a dedicated set of Enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing Enzymes are well characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila lacks a gene for carboxypeptidase E (CPE), a Key Enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of Drosophila carboxypeptidase D (dCPD) in global neuropeptide processing and selected peptide-regulated behaviours. We found that a deficiency in dCPD results in C-terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD-encoding gene silver in the larva causes lethality, and leads to deficits in adult starvation-induced hyperactivity and appetitive gustatory preference, as well as to reduced survival rate and activity levels. A phylogenomic analysis suggests that loss of CPE is not a common insect feature, but specifically occured in Hymenoptera and Diptera. Our results show that dCPD is a Key Enzyme for neuropeptide processing in Drosophila, and is required for proper peptide-regulated behaviour. dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. Our results raise the question why Drosophila and other Diptera and Hymenoptera, unlike other insects, obviously have lost the gene for CPE but kept a gene encoding CPD.
