Neuropilin is a neuronal cell surface protein and has been shown to function as a receptor for a secreted protein, semaphorin III/D, that can induce neuronal growth cone collapse and repulsion of neurites in vitro. The roles of neuropilin in vivo, however, are unknown. Here, we report that neuropilin-deficient mutant mice produced by targeted disruption of the neuropilin gene show severe abnormalities in the trajectory of efferent fibers of the PNS. We also describe that neuropilin-deprived dorsal root ganglion neurons are perfectly protected from growth cone collapse elicited by semaphorin III/D. Our results indicate that neuropilin-semaphorin III/D-mediated chemorepulsive signals play a major role in guidance of PNS efferents.
Hippocampal mossy fibers project preferentially to the stratum lucidum, the proximal-most lamina of the suprapyramidal region of CA3. The molecular mechanisms that govern this lamina-restricted projection are still unknown. We examined the projection pattern of mossy fibers in mutant mice for semaphorin receptors plexin-A2 and plexin-A4, and their ligand, the transmembrane semaphorin Sema6A. We found that plexin-A2 deficiency causes a shift of mossy fibers from the suprapyramidal region to the infra- and intrapyramidal regions, while plexin-A4 deficiency induces inappropriate spreading of mossy fibers within CA3. We also report that the plexin-A2 loss-of-function phenotype is genetically suppressed by Sema6A loss of function. Based on these results, we propose a model for the lamina-restricted projection of mossy fibers: the expression of plexin-A4 on mossy fibers prevents them from entering the Sema6A-expressing suprapyramidal region of CA3 and restricts them to the proximal-most part, where Sema6A repulsive activity is attenuated by plexin-A2.
It has been proposed that four members of the plexin A subfamily (plexin-As; plexin-A1, -A2, -A3, and -A4) and two neuropilins (neuropilin-1 and neuropilin-2) form complexes and serve as receptors for class 3 secreted semaphorins (Semas), potent neural chemorepellents. The roles of given plexin-As in semaphorin signaling and axon guidance, however, are mostly unknown. Here, to elucidate functions of plexin-A4 in semaphorin signaling and axon guidance events in vivo, we generated plexin-A4 null mutant mice by targeted disruption of the plexin-A4 gene. Plexin-A4 mutant mice were defective in the trajectory and projection of peripheral sensory axons and sympathetic ganglion (SG) axons and the formation of the anterior commissure and the barrels. The defects in peripheral sensory and SG axons were fundamentally related to those of neuropilin-1 or Sema3A mutant embryos reported but were more moderate than the phenotype in these mutants. The growth cone collapse assay showed that dorsal root ganglion axons and SG axons of plexin-A4 mutant embryos partially lost their responsiveness to Sema3A. These results suggest that plexin-A4 plays roles in the propagation of Sema3A activities and regulation of axon guidance and that other members of the plexin-A subfamily are also involved in the propagation of Sema3A activities. Plexin-A4-deficient SG axons did not lose their responsiveness to Sema3F, suggesting that plexin-A4 serves as a Sema3A-specific receptor, at least in SG axons. In addition, the present study showed that plexin-A4 bound class 6 transmembrane semaphorins, Sema6A and Sema6B, and mediated their axon-repulsive activities, independently of neuropilin-1. Our results imply that plexin-A4 mediates multiple semaphorin signals and regulates axon guidance in vivo.
Organic matter (OM) is present in most terrestrial environments and is often found coprecipitated with ferrihydrite (Fh). Sorption or coprecipitation of OM with Fe oxides has been proposed to be an important mechanism for long-term C preservation. However, little is known about the impact of coprecipitated OM on reductive dissolution and transformation of Fe(III) (oxyhydr)oxides. Thus, we study the effect of humic acid (HA) coprecipitation on Fh reduction and secondary mineral formation by the dissimilatory Fe(III)-reducing bacterium Shewanella putrefaciens strain CN32. Despite similar crystal structure for all coprecipitates investigated, resembling 2-line Fh, the presence of coprecipitated HA resulted in lower specific surface areas. In terms of reactivity, coprecipitated HA resulted in slower Fh bioreduction rates at low C/Fe ratios (i.e., C/Fe ≤ 0.8), while high C/Fe ratios (i.e., C/Fe ≥ 1.8) enhanced the extent of bioreduction compared to pure Fh. The coprecipitated HA also altered the secondary Fe mineralization pathway by inhibiting goethite formation, reducing the amount of magnetite formation, and increasing the formation of a green rust-like phase. This study indicates that coprecipitated OM may influence the rates, pathway, and mineralogy of biogeochemical Fe cycling and anaerobic Fe respiration within soils.
Neuropilin (previously known as the A5 protein) is a membrane protein identified in Xenopus and is presumed to be involved in the target recognition of the optic nerve fibers. We have isolated cDNAs encoding the chick homologue of neuropilin, using the Xenopus neuropilin cDNA as a hybridization probe. The predicted amino acid sequence of chick neuropilin is 75% identical to that of the Xenopus homologue. A cell aggregation assay showed that fibroblasts transfected with the chick neuropilin cDNA acquired cell adhesiveness. This adhesion is mediated by a heterophilic interaction between neuropilin and protease-sensitive molecules on fibroblasts. The expression of chick neuropilin is restricted to certain neuronal circuits and is dynamically regulated during development, as is the Xenopus homologue. However, their expression patterns differed significantly in the visual systems between the two species: In the chick optic tectum, the localization of neuropilin is confined to layers d and e of SGFS, two of the six layers receiving the retinal input; the chick optic nerve fibers do not express neuropilin; in the chick retina, amacrine cells transiently express neuropilin. Cultured neurons of the dorsal root ganglia express chick neuropilin on their neurites including growth cones. These results suggests that neuropilin functions as a cell adhesion molecule during the formation of certain neuronal circuits in vivo.
There is increasing interest in the unique biological and medical properties of carbon nanotubes (CNTs), and it is expected that biomaterials incorporating CNTs will be developed for clinical use. There has been a great deal of progress in improving the various properties of CNTs for use in biomaterials and for promotion of tissue regeneration as scaffold materials. The effects of CNTs on cells and tissues are extremely important for their use in biomaterials. This tutorial review clarifies the current state of knowledge in the interdisciplinary field of CNT-based nanobiotechnology to determine whether CNTs may be useful in biomaterials. Future perspectives in this rapidly developing field will also be discussed.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.