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571.
Cxcl12/Cxcr4 chemokine signaling is required for placode assembly and sensory axon pathfinding in the zebrafish olfactory system 总被引:2,自引:0,他引:2
Positioning neurons in the right places and wiring axons to the appropriate targets are essential events for establishment of neural circuits. In the zebrafish olfactory system, precursors of olfactory sensory neurons (OSNs) assemble into a compact cluster to form the olfactory placode. Subsequently, OSNs differentiate and extend their axons to the presumptive olfactory bulb with high precision. In this study, we aim to elucidate the molecular mechanism underlying these two developmental processes. cxcr4b, encoding a chemokine receptor, is expressed in the migrating olfactory placodal precursors, and cxcl12a (SDF-1a), encoding a ligand for Cxcr4b, is expressed in the abutting anterior neural plate. The expression of cxcr4b persists in the olfactory placode at the initial phase of OSN axon pathfinding. At this time, cxcl12a is expressed along the placode-telencephalon border and at the anterior tip of the telencephalon, prefiguring the route and target of OSN axons, respectively. Interfering with Cxcl12a/Cxcr4b signaling perturbs the assembly of the olfactory placode, resulting in the appearance of ventrally displaced olfactory neurons. Moreover, OSN axons frequently fail to exit the olfactory placode and accumulate near the placode-telencephalon border in the absence of Cxcr4b-mediated signaling. These data indicate that chemokine signaling contributes to both the olfactory placode assembly and the OSN axon pathfinding in zebrafish. 相似文献
572.
573.
Toru Yoshihara Kazushi Sugihara Yasuhiko Kizuka Shogo Oka Masahide Asano 《The Journal of biological chemistry》2009,284(18):12550-12561
The glycosylation of glycoproteins and glycolipids is important for central
nervous system development and function. Although the roles of several
carbohydrate epitopes in the central nervous system, including polysialic
acid, the human natural killer-1 (HNK-1) carbohydrate, α2,3-sialic acid,
and oligomannosides, have been investigated, those of the glycan backbone
structures, such as Galβ1-4GlcNAc and Galβ1-3GlcNAc, are not fully
examined. Here we report the generation of mice deficient in
β4-galactosyltransferase-II (β4GalT-II). This galactosyltransferase
transfers Gal from UDP-Gal to a nonreducing terminal GlcNAc to synthesize the
Gal β1-4GlcNAc structure, and it is strongly expressed in the central
nervous system. In behavioral tests, the β4GalT-II-/- mice
showed normal spontaneous activity in a novel environment, but impaired
spatial learning/memory and motor coordination/learning. Immunohistochemistry
showed that the amount of HNK-1 carbohydrate was markedly decreased in the
brain of β4GalT-II-/- mice, whereas the expression of
polysialic acid was not affected. Furthermore, mice deficient in
glucuronyltransferase (GlcAT-P), which is responsible for the biosynthesis of
the HNK-1 carbohydrate, also showed impaired spatial learning/memory as
described in our previous report, although their motor coordination/learning
was normal as shown in this study. Histological examination showed abnormal
alignment and reduced number of Purkinje cells in the cerebellum of
β4GalT-II-/- mice. These results suggest that the
Galβ1-4GlcNAc structure in the HNK-1 carbohydrate is mainly synthesized
by β4GalT-II and that the glycans synthesized by β4GalT-II have
essential roles in higher brain functions, including some that are
HNK-1-dependent and some that are not.The glycosylation of glycoproteins, proteoglycans, and glycolipids is
important for their biological activities, stability, transport, and clearance
from circulation, and cell-surface glycans participate in cell-cell and
cell-extracellular matrix interactions. In the central nervous system, several
specific carbohydrate epitopes, including polysialic acid
(PSA),3 the
human natural killer-1 (HNK-1) carbohydrate, α2,3-sialic acid, and
oligomannosides play indispensable roles in neuronal generation, cell
migration, axonal outgrowth, and synaptic plasticity
(1). Functional analyses of the
glycan backbone structures, like lactosamine core (Galβ1-4GlcNAc),
neolactosamine core (Galβ1-3GlcNAc), and polylactosamine
(Galβ1-4GlcNAcβ1-3) have been carried out using gene-deficient mice
in β4-galactosyltransferase-I (β4GalT-I)
(2,
3), β4GalT-V
(4),
β3-N-acetylglucosaminyl-transferase-II (β3GnT-II)
(5), β3GnT-III
(Core1-β3GnT) (6),
β3GnT-V (7), and Core2GnT
(8). However, the roles of
these glycan backbone structures in the nervous system have not been examined
except the olfactory sensory system
(9).β4GalTs synthesize the Galβ1-4GlcNAc structure via the
β4-galactosylation of glycoproteins and glycolipids; the β4GalTs
transfer galactose (Gal) from UDP-Gal to a nonreducing terminal
N-acetylglucosamine (GlcNAc) of N- and O-glycans
with a β-1,4-linkage. The β4GalT family has seven members
(β4GalT-I to VII), of which at least five have similar
Galβ1-4GlcNAc-synthesizing activities
(10,
11). Each β4GalT has a
tissue-specific expression pattern and substrate specificity with overlapping,
suggesting each β4GalT has its own biological role as well as redundant
functions. β4GalT-I and β4GalT-II share the highest identity (52% at
the amino acid level) among the β4GalTs
(12), suggesting these two
galactosyltransferases can compensate for each other. β4GalT-I is
strongly and ubiquitously expressed in various non-neural tissues, whereas
β4GalT-II is strongly expressed in neural tissues
(13,
14). Indeed, the β4GalT
activity in the brain of β4GalT-I-deficient (β4GalT-I-/-)
mice remains as high as 65% of that of wild-type mice, and the expression
levels of PSA and the HNK-1 carbohydrate in the brain of these mice are normal
(15). These results suggest
β4GalTs other than β4GalT-I, like β4GalT-II, are important in
the nervous system.Among the β4GalT family members, only β4GalT-I-/- mice
have been examined extensively; this was done by us and another group. We
reported that glycans synthesized by β4GalT-I play various roles in
epithelial cell growth and differentiation, inflammatory responses, skin wound
healing, and IgA nephropathy development
(2,
16-18).
Another group reported that glycans synthesized by β4GalT-I are involved
in anterior pituitary hormone function and in fertilization
(3,
19). However, no other nervous
system deficits have been reported in these mice, and the role of the
β4-galactosylation of glycoproteins and glycolipids in the nervous system
has not been fully examined.In this study, we generated β4GalT-II-/- mice and examined
them for behavioral abnormalities and biochemical and histological changes in
the central nervous system. β4GalT-II-/- mice were impaired in
spatial learning/memory and motor coordination/learning. The amount of HNK-1
carbohydrate was markedly decreased in the β4GalT-II-/- brain,
but PSA expression was not affected. These results suggest that the
Galβ1-4GlcNAc structure in the HNK-1 carbohydrate is mainly synthesized
by β4GalT-II and that glycans synthesized by β4GalT-II have
essential roles in higher brain functions, including ones that are HNK-1
carbohydrate-dependent and ones that are independent of HNK-1. 相似文献
574.
Kazuko Tsuchihara Tetsuichi Wazawa Toshio Yanagida Xiang-Guo Zheng Kazuo Yoshihara Fumio Tokunaga 《FEBS letters》2009,583(2):345-349
A native female-specific chemoreceptive protein of a swallowtail butterfly [oviposition stimulant binding protein (OSBP)] was shown to specifically bind to aristolochic acid, a main stimulant for oviposition from its host plant. Oviposition stimulants are recognized by chemoreceptive organs of insects. OSBP isolated previously from the chemoreceptive organs was assumed to bind to an oviposition stimulant. Using a highly sensitive fluorescent micro-binding assay, we clarified OSBP bound to aristolochic acid. Three-dimensional molecular modeling revealed the structure of the OSBP-aristolochic acid complex. This is the first report of a native chemoreceptive protein binding to an oviposition stimulant as a ligand in insects. 相似文献
575.
576.
577.
Aichi M Yoshihara S Yamashita M Maeda S Nagai K Omata T 《Bioscience, biotechnology, and biochemistry》2006,70(11):2682-2689
The products of the NpR1527 and NpR1526 genes of the filamentous, diazotrophic, fresh-water cyanobacterium Nostoc punctiforme strain ATCC 29133 were identified as a nitrate transporter (NRT) and nitrate reductase (NR) respectively, by complementation of nitrate assimilation mutants of the cyanobacterium Synechococcus elongatus strain PCC 7942. While other fresh-water cyanobacteria, including S. elongatus, have an ATP-binding cassette (ABC)-type NRT, the NRT of N. punctiforme belongs to the major facilitator superfamily, being orthologous to the one found in marine cyanobacteria (NrtP). Unlike the ABC-type NRT, which transports both nitrate and nitrite with high affinity, Nostoc NrtP transported nitrate preferentially over nitrite. NrtP was distinct from ABC-type NRT also in its insensitivity to ammonium-promoted regulation at the post-translational level. The nitrate reductase of N. punctiforme was, on the other hand, inhibited upon addition of ammonium to medium, lending ammonium sensitivity to nitrate assimilation. 相似文献
578.
579.
Wang J Ohshima T Yasunari U Namikoshi S Yoshihara A Miyazaki H Maeda N 《Gerodontology》2006,23(3):157-163
Objectives: To screen the carriage status of Candida species, especially Candida albicans and its genotype in an epidemiological survey and to investigate its correlation with the dental, periodontal and prosthetic status of healthy elderly subjects. Materials and methods: Microbiological samples were collected from the dorsum of the tongue of 366 subjects, aged 75, and cultured on CHROMagar medium. The carriage status of Candida spp. and the distribution of C. albicans genotypes by a polymerase chain reaction (PCR) method were analysed and compared with the dental, periodontal and prosthetic status of the subjects. Results: A high carriage rate (68.6%) of Candida spp. and the predominant species of C. albicans (72.1%) were found in this study. The prevalence, density and multi‐species of Candida spp. were significantly related to the presence of a dental prosthesis. In C. albicans, genotype A predominated (56.4%) and genotype D showed a higher prevalence (12.5%) than previous reports. When comparing Candida spp. carriage with the oral status, significant positive correlations were found with the presence of any dental prosthesis, missing teeth, the number of retained roots and the percentage of sites showing bleeding on probing (BOP), while significant negative correlations were found with the number of teeth present, sound and filled teeth. Conclusions: Candida carriage on the dorsum of the tongue in healthy elderly is significantly associated with the dental, periodontal and prosthetic status, especially the presence of a dental prosthesis. As the complexity of the prosthesis being worn increased, the relative risk of Candida carriage and the numbers and multi‐species of Candida increased accordingly. 相似文献
580.
Nishimura M Ookawara T Eguchi H Fujiwara N Yoshihara D Yasuda J Mimura O Suzuki K 《Free radical research》2006,40(6):589-595
Both extracellular superoxide dismsutase (EC-SOD) and heparin binding EGF like growth factor (HB-EGF) are produced in smooth muscle cells of the arterial wall, and are thought to play pathological roles in atherosclerosis with heparin binding characteristics. EC-SOD treatment clearly reduced the H2O2 induced expression of HB-EGF in rat aortic smooth muscle cells (RASMC). EC-SOD also inhibited the induction of HB-EGF by 12-O-tetradecanoylphorbol-13-acetate (TPA) in RASMC by 60%. Both H2O2 and TPA increased intracellular ROS levels, and EC-SOD inhibited ROS generation only for the case of H2O2 but not TPA. Treatment of the cells with heparin alone decreased HB-EGF expression by 20%, whereas EC-SOD alone and a co-incubation with EC-SOD and heparin suppressed the induction by 60 and 70%, respectively. These results suggest that EC-SOD is related to the EGF signaling in two ways, competition for HSPG with HB-EGF and as an ROS scavenger. 相似文献