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      Call for Papers: Sex and Gender in Neurodegenerative Diseases

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      About Neurodegenerative Diseases: 3.0 Impact Factor I 4.3 CiteScore I 0.695 Scimago Journal & Country Rank (SJR)

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      Evolution of the neurotrophin signaling system in invertebrates.

      Brain, Behavior and Evolution
      Animals, Base Sequence, Evolution, Molecular, Humans, Invertebrates, genetics, physiology, Molecular Sequence Data, Nerve Growth Factors, metabolism, Receptors, Nerve Growth Factor, classification, Sequence Alignment, Sequence Homology, Signal Transduction

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          Abstract

          Nucleotide sequences encoding orthologs of neurotrophins and their receptors, p75(NTR) and Trk receptors, have been identified in the sea urchin Strongylocentrotus purpuratus, and the acorn worm, Saccoglossus kowalevskii, whereas the ascidian (sea squirt) species Ciona intestinalis and Ciona savignii appear to lack such orthologs. These results suggest that a functional neurotrophin system was already present at the beginning of deuterostome evolution, but was lost in ascidians. Remarkably, it appears that evolution of a p75(NTR) ortholog represented one of the earliest events in the expansion of the tumor necrosis factor receptor superfamily.

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          Tunicates and not cephalochordates are the closest living relatives of vertebrates.

          Tunicates or urochordates (appendicularians, salps and sea squirts), cephalochordates (lancelets) and vertebrates (including lamprey and hagfish) constitute the three extant groups of chordate animals. Traditionally, cephalochordates are considered as the closest living relatives of vertebrates, with tunicates representing the earliest chordate lineage. This view is mainly justified by overall morphological similarities and an apparently increased complexity in cephalochordates and vertebrates relative to tunicates. Despite their critical importance for understanding the origins of vertebrates, phylogenetic studies of chordate relationships have provided equivocal results. Taking advantage of the genome sequencing of the appendicularian Oikopleura dioica, we assembled a phylogenomic data set of 146 nuclear genes (33,800 unambiguously aligned amino acids) from 14 deuterostomes and 24 other slowly evolving species as an outgroup. Here we show that phylogenetic analyses of this data set provide compelling evidence that tunicates, and not cephalochordates, represent the closest living relatives of vertebrates. Chordate monophyly remains uncertain because cephalochordates, albeit with a non-significant statistical support, surprisingly grouped with echinoderms, a hypothesis that needs to be tested with additional data. This new phylogenetic scheme prompts a reappraisal of both morphological and palaeontological data and has important implications for the interpretation of developmental and genomic studies in which tunicates and cephalochordates are used as model animals.
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            P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp.

            In inhibiting neurite outgrowth, several myelin components, including the extracellular domain of Nogo-A (Nogo-66), oligodendrocyte myelin glycoprotein (OMgp) and myelin-associated glycoprotein (MAG), exert their effects through the same Nogo receptor (NgR). The glycosyl phosphatidylinositol (GPI)-anchored nature of NgR indicates the requirement for additional transmembrane protein(s) to transduce the inhibitory signals into the interior of responding neurons. Here, we demonstrate that p75, a transmembrane protein known to be a receptor for the neurotrophin family of growth factors, specifically interacts with NgR. p75 is required for NgR-mediated signalling, as neurons from p75 knockout mice are no longer responsive to myelin and to each of the known NgR ligands. Blocking the p75-NgR interaction also reduces the activities of these inhibitors. Moreover, a truncated p75 protein lacking the intracellular domain, when overexpressed in primary neurons, attenuates the same set of inhibitory activities, suggesting that p75 is a signal transducer of the NgR-p75 receptor complex. Thus, interfering with p75 and its downstream signalling pathways may allow lesioned axons to overcome most of the inhibitory activities associated with central nervous system myelin.
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              Molecular phylogeny and divergence times of deuterostome animals.

              The phylogenetic relationships among deuterostome animals have been debated for many years, and a diversity of hypotheses have been proposed based on both morphological and molecular data. Here we have assembled sequences of 217 nuclear-encoded proteins to address specific questions concerning their relationships and times of origin. We recovered significant support for urochordates as the closest relative of vertebrates with an analysis of 59 proteins (17,400 amino acids) and suggest that the basal position of urochordates found in previous molecular studies may have been the result of long-branch attraction biases. Our results also support Ambulacraria, the pairing of hemichordates with echinoderms (nine proteins; 2,382 amino acids), and Cyclostomata, the pairing of lampreys with hagfish (25 proteins; 6,895 amino acids). In addition, 325 shared proteins (102,110 amino acids) were obtained from the complete genomes of six vertebrates and a urochordate for phylogenetic analysis and divergence time estimation. An evolutionary timescale was estimated using a local (Bayesian) molecular clock method. We found that most major lineages of deuterostomes arose prior to the Cambrian Explosion of fossils (approximately 520 MYA) and that several lineages had originated before periods of global glaciation in the Precambrian.
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