| 1. |
- Agerman, K, et al.
(författare)
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BDNF gene replacement reveals multiple mechanisms for establishing neurotrophin specificity during sensory nervous system development
- 2003
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Ingår i: Development (Cambridge, England). - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 130:8, s. 1479-1491
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Tidskriftsartikel (refereegranskat)abstract
- Neurotrophins have multiple functions during peripheral nervous system development such as controlling neuronal survival, target innervation and synaptogenesis. Neurotrophin specificity has been attributed to the selective expression of the Trk tyrosine kinase receptors in different neuronal subpopulations. However, despite overlapping expression of TrkB and TrkC in many sensory ganglia, brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) null mutant mice display selective losses in neuronal subpopulations. In the present study we have replaced the coding part of theBDNF gene in mice with that of NT3 (BDNFNT3/NT3)to analyse the specificity and selective roles of BDNF and NT3 during development. Analysis of BDNFNT3/NT3 mice showed striking differences in the ability of NT3 to promote survival, short-range innervation and synaptogenesis in different sensory systems. In the cochlea, specificity is achieved by a tightly controlled spatial and temporal ligand expression. In the vestibular system TrkB or TrkC activation is sufficient to promote vestibular ganglion neuron survival, while TrkB activation is required to promote proper innervation and synaptogenesis. In the gustatory system, NT3 is unable to replace the actions of BDNF possibly because of a temporally selective expression of TrkB in taste neurons. We conclude that there is no general mechanism by which neurotrophin specificity is attained and that specificity is achieved by (i) a tightly controlled spatial and temporal expression of ligands, (ii) different Trk receptors playing distinct roles within the same neuronal subpopulation, or (iii) selective receptor expression in sensory neuron subpopulations.
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| 2. |
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| 3. |
- Houzelstein, D, et al.
(författare)
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Phylogenetic analysis of the vertebrate galectin family
- 2004
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Ingår i: Molecular biology and evolution. - : Oxford University Press (OUP). - 0737-4038 .- 1537-1719. ; 21:7, s. 1177-1187
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Tidskriftsartikel (refereegranskat)abstract
- Galectins form a family of structurally related carbohydrate binding proteins (lectins) that have been identified in a large variety of metazoan phyla. They are involved in many biological processes such as morphogenesis, control of cell death, immunological response, and cancer. To elucidate the evolutionary history of galectins and galectin-like proteins in chordates, we have exploited three independent lines of evidence: (i) location of galectin encoding genes (LGALS) in the human genome; (ii) exon-intron organization of galectin encoding genes; and (iii) sequence comparison of carbohydrate recognition domains (CRDs) of chordate galectins. Our results suggest that a duplication of a mono-CRD galectin gene gave rise to an original bi-CRD galectin gene, before or early in chordate evolution. The N-terminal and C-terminal CRDs of this original galectin subsequently diverged into two different subtypes, defined by exon-intron structure (F4-CRD and F3-CRD). We show that all vertebrate mono-CRD galectins known to date belong to either the F3- or F4-subtype. A sequence of duplication and divergence events of the different galectins in chordates is proposed.
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| 4. |
- Umemoto, K, et al.
(författare)
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Conformational differences in liganded and unliganded states of Galectin-3
- 2003
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Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 42:13, s. 3688-3695
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Tidskriftsartikel (refereegranskat)abstract
- The conformation of the carbohydrate recognition domain of Galectin-3, a lectin known to bind galactose containing oligosaccharides in mammalian systems, has been investigated in the absence of ligand and in the presence of N-acetylactosamine. A new methodology based on the measurement of residual dipolar couplings from NMR spectra has been used to characterize differences in protein structure along the backbone in the presence and absence of ligand, as well as the binding geometry of the ligand itself. The data on the ligand are consistent with the ligand binding geometry found in a crystal structure of the complexed state. However, a significant rearrangement of backbone loops near the binding site appears to occur in the absence of ligand. The implications for ligand specificity and protein functionality are discussed.
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