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1 Group of Neurobiology, School of Allied Health Sciences, Osaka University Faculty of Medicine, Yamadaoka 1-7, Suita, Osaka 565-0871, Japan
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Department of Molecular Genetic Research, National Institute of Longevity Sciences, Morioka-cho, Ohbu, Aichi 474-5822, Japan
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Introduction |
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500 amino acids (Kolodkin et al. 1993; Tessier-Lavigne & Goodman 1996; Semaphorin Nomenclature Committee 1999). The secreted forms of semaphorins have been implicated in mediating axonal guidance in the developing nervous system (Tessier-Lavigne & Goodman 1996; Taniguchi et al. 1997). In vitro, several semaphorins act as potent repulsive molecules (Luo et al. 1993; Messersmith et al. 1995; Miyazaki et al. 1999a, 1999b), but at least some semaphorins are bifunctional molecules that function as chemoattractants as well as chemorepellents. For example, Sema3A induces growth cone collapse of dorsal root ganglion (DRG) neurones and cortical axons, while it acts as an attractant for cortical apical dendrites (Polleux et al. 2000). Sema3C (formerly called SemE) repels sympathetic axons but attracts cortical axons in vitro (Bagnard et al. 1998). We have also shown that Sema3E (primarily called M-SemaH) repels and inhibits axon outgrowth in DRG neurones, whereas in rat pheochromocytoma cell line (PC12 cells) it induces neurite outgrowth (Miyazaki et al. 1999a; Sakai et al. 1999). In grasshopper embryos, Ti1 axons are initially repelled by an invertebrate secreted-semaphorin, Sema2a, until they encounter a stripe of epithelial cells that express an invertebrate transmembrane-semaphorin, Sema1a (Tessier-Lavigne & Goodman 1996). In vivo in invertebrates, a secreted-semaphorin acts as a repulsive factor in axon guidance, while a transmembrane-semaphorin can promote axon outgrowth (Wong et al. 1999). However, the functions of numerous transmembrane-semaphorins in the vertebrate nervous system are largely unknown. A mammalian transmembrane-member, Sema4D, is proteolytically digested and shed from immune cells (Delaire et al. 2001), and soluble Sema4D promotes immune responses, proliferation and viability of lymphocytes (Hall et al. 1996), while yet little is known in the nervous system. Recently, we have shown that soluble Sema4D is neurotrophic to enhance neurite outgrowth of PC12 cells, which are well known to differentiate into neural cells in response to NGF (Fujioka et al. 2003). Herein we have investigated whether soluble Sema4D retracts axonal outgrowth of DRG neurones as Sema3E does (Sakai et al. 1999). Instead of repulsive effect, Sema4D promotes axonal outgrowth of DRG neurones in the absence of NGF. We demonstrate what is involved in this Sema4D-action, and whether Sema4D could function in an autocrine/paracrine manner. |
Results |
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We previously reported that a secreted type of semaphorin, Sema3E, induced neurite outgrowth of PC12 cells in a NGF-independent manner (Sakai et al. 1999). Meanwhile in DRG neurones, it acted as a repulsive factor to collapse growth cones and retract axons (Miyazaki et al. 1999a, 1999b), suggesting the diversity of semaphorin signals. We recently showed that soluble forms of Sema4D enhanced neurite outgrowth of PC12 cells in a NGF-dependent manner (Fujioka et al. 2003). In this study we have examined whether Sema4D can retract or stimulate axonal outgrowth of DRG neurones as Sema 3E. Sema4D-AP (1 nM) alone in the absence of NGF stimulated axonal outgrowth of DRG neurones (Fig. 1A,B). Sema4D-AP in the presence of NGF (50 ng/mL) also enhanced axonal outgrowth of DRG neurones. When DRG neurones were incubated in the Sema4D-medium pretreated with IgGs prepared from the polyclonal antiserum against Sema4Ded (anti-Sema4D) at 1 : 50 dilution, Sema4D-AP-induced-axonal outgrowth disappeared almost completely, while control IgGs from preimmune serum at the same dilution did not inhibit axonal outgrowth-action of Sema4D-AP (Fig. 1C). Preimmune and anti-Sema4D IgGs at this concentration was not acting in a toxic fashion, as we observed no morphologic evidence of toxicity in the cells when the cells are exposed to anti-Sema4D. This result supported that Sema4D itself induced axonal outgrowth of DRG neurones. We also investigated whether immobilized-Sema4D could stimulate axonal outgrowth of DRG neurones by culturing these cells on Sema4D-AP-coated dishes. No outgrowth-action was induced with immobilized-Sema4D (data not shown).
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Sema4D could not stimulate neurite-outgrowth of PC12 cells when NGF was not added to the culture, and thus neurite-outgrowth action of Sema4D on PC12 cells was NGF-dependent. On the other hand, Sema4D alone induced axonal outgrowth of DRG neurones, suggesting that Sema4D-action on DRG neurones was NGF-independent. However, in our DRG-neurone culture there were Schwann cells scattered among ganglionic neurones. Since Schwann cells could produce growth factors such as NGF (Matsuoka et al. 1991), it can be conceivable that such low-level of growth factors could cause the discrepancy in NGF-dependency of Sema4D-action between DRG neurones and PC12 cells. To investigate whether the action of Sema4D is dependent on endogenously produced-NGF in DRG culture, we used antibodies to NGF. Deprivation of endogenous NGF by adding anti-NGF antibodies markedly inhibited axonal outgrowth-action of Sema4D in a dose-dependent manner (Fig. 2A). NGF depletion by the antibodies to NGF had no toxic effect or no significant effect on axonal outgrowth of DRG neurones in the absence of Sema4D. The results suggest that endogenously produced-low-level of NGF be likely involved in Sema4D-action.
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Endogenous Sema4D is expressed in DRG neurones
In situ hybridization histochemistry showed strong expression of Sema4D transcripts in the DRGs of mouse embryos at E11.5 and E14.5 (Fig. 3A,B). Sema4D signals were detected in almost all DRG cells. The transcripts were also found in scattered cells of the ventral parts of embryonic spinal cords (Fig. 3A). Immunohistochemical staining using the antibody to Sema4D showed intense staining in the central and peripheral axons extending from DRGs as well as in the spinal nerves, but weak to moderate staining in cell bodies of DRG neurones (Fig. 3C,D). These results suggest that Sema4D proteins produced in DRG neurones be transported to their axonal processes.
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Plexin-B1 is suggested to be a high affinity receptor for Sema4D (Tamagnone et al. 1999). To investigate whether plexin-B1 is a specific receptor for Sema4D, we performed binding experiments by using Sema4D-AP as a ligand. The cells were transiently transfected with expression vectors encoding plexin-B1, plexin-B2, neuropilin-1, and neuropilin-2. The last two, neuropilin-1 and neuropilin-2, are high affinity receptors for type 3 semaphorins (He & Tessier-Lavigne 1997; Fujisawa & Kitsukawa 1998). One nM of Sema4D-AP bound either the cell expressing plexin-B1 or plexin-B2, but neither the cell expressing neuropilin-1 nor neuropilin-2 (Fig. 4A–D). Therefore both plexin-B1 and plexin-B2, but not neuropilin-1 nor neuropilin-2, are candidates for Sema4D receptors. Then we investigated whether the addition of plexin-B1 or B2 could inhibit Sema4D-neurite outgrowth action of PC12 cells using crude membrane fractions of transfectants. Neurite-outgrowth actions of Sema4D was significantly inhibited by membrane fractions from plexin-B1 or plexin-B2 transfectants, but not by the fractions from mock-control cells transfected with its parent expression vector (Fig. 4E,F).
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In situ hybridization histochemistry showed that mRNAs for plexin-B1 and B2 were expressed in embryonic DRGs (Fig. 5A,C), but sense cRNA probes for these plexins (for the control) showed no specific signals (Fig. 5B,D). It was hard to identify which cells of the DRG express the signals in these autoradiograms. Immunostaining with antibodies to plexin-B1 and B2 were also found in spinal roots and nerves (Fig. 5E). RT-PCR products for plexin-B1 and B2 were detected from cDNA of embryonic DRGs and PC12 cells as well as the brain. On the other hand, RT-PCR products for CD72, a low-affinity-Sema4D receptor of immune cells (Kumanogoh et al. 2000), were not detected from DRGs nor PC12 cells but were detected from the spleen and thymus (Fig. 5F). These results indicate that embryonic DRG neurones most likely express mRNAs for plexin-B1 and plexin-B2, and produce these proteins to transport toward their axonal processes, but do not express CD72.
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Discussion |
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In this study, we have shown that Sema4D enhances axonal outgrowth of DRG neurones either alone or in the presence of NGF. On the other hand, in PC12 cells Sema4D alone could not induce neurite outgrowth (Fujioka et al. 2003). However, endogenous-NGF-deprivation by using the antibodies to NGF and inhibition of NGF-signalling using a TrkA-inhibitor K252a markedly reduced Sema4D-induced axonal outgrowth in DRG neurones. These results suggest that such Sema4D-action on DRG neurones is also dependent of endogenous NGF and its downstream-signalling as found on PC12 cells, although the effect on heterogeneous cell population in DRG-culture and that on clonal PC12 cells cannot be directly compared. In our previous study, inhibition of TrkA kinase activity by K252a also reduced NGF-dependent-Sema4D action of neurite outgrowth in PC12 cells in the presence of NGF. The inhibition of neurite outgrowth activity by K252a was incomplete in PC12 cells, while almost complete inhibition was seen in DRG neurones. It appears to be difficult to explain this discrepancy, but some difference of experimental conditions might have caused such discrepancy as follows: 50 ng/mL of NGF was added to PC 12 cell-culture for Sema4D-acitivity assay, while no NGF was added to DRG neurone-culture since Sema4D can promote neurite outgrowth without addition of NGF in DRG neurones. K252a almost completely inhibited NGF alone-induced Trk-activation (PC12 cells) or Sema4D-plus-low level of endogenous-NGF-induced Trk-activation (DRG neurones). However, it might not be enough to inhibit completely Sema4D-plus-high level of NGF-induced Trk activation (PC12 cells), although future studies would be necessary. Sema4D dramatically increases the sensitivity of PC12 cells to NGF, and thus cells respond to very low concentrations of NGF such as 0.1–1 ng/mL that alone does not induce any marked neural differentiation (Fujioka et al. 2003). Since Schwann cells produce NGF (Matsuoka et al. 1991), the contamination of these cells in our DRG-neurone culture might explain such Sema4D-action on DRG neurones. Sema4D appears to be extremely potent in accelerating the velocity of neurite outgrowth induced by NGF in DRG cells most likely as in PC12 cells.
Bifunctional guidance cues
Precise axon guidance is the consequence of a continuous reorganization of actin filament structures in response to repulsive and attractive cues such as netrins, brain-derived neurotrophic factor (BDNF), Slits, semaphorins, and ephrins (reviewed by Dickson 2002). Extracellular guidance cues instruct the growth cone to advance, retract or turn. In a popular model, attractive guidance cues promote growth cone advance, whereas repulsive cues inhibit neurite growth or induce retraction (Mueller 1999). Netrin-1 and BDNF normally trigger an attractive response of the growth cones of Xenopus spinal neurones, but induce repulsive response of these growth cones in the presence of a competitive analogue of cAMP or of a specific inhibitor of protein kinase A (Song & Poo 1999). In vivo, Xenopus retinal axons are first attracted out of the eye by netrin-1 at the optic nerve head, become indifferent to it as they grow through the ventral diencephalon, and finally are repelled by netrin-1 once they reach the tectum (Shewan et al. 2002), and these changes correlate with a gradual decline in cAMP levels. Likewise, Sema3A can convert axonal responses from repulsion to attraction by raising levels of cGMP; Sema3A attracts the apical dendrites of pyramidal neurones toward the cortical plate but repels the axons away from it. Guanylyl cyclase is specifically localized in dendrites, implying that cGMP levels may be higher in dendrites than in axons (Polleux et al. 2000). These suggest that axon guidance cues including semaphorins are bifunctional to growth cone response depending on intracellular and extracellular environments. It is conceivable that the different cellular environment including cAMP/cGMP levels induces the opposing responses to Sema4D between embryonic DRG and hippocampal neurones (Swiercz et al. 2002). It was not clear why coated-immobilized Sema4D had no effect on neurite outgrowth of DRG neurones. However, the concentration of Sema4D-ligand coated on dishes might not be enough to induce the response of DRG neurones, or aggregation of the ligand might be required for the response.
Sema4D receptors in DRG neurones
There are at least two distinct types of vertebrate semaphorin receptors, plexins and neuropilins, which can interact to form receptor complexes. Neuropilins bind to secreted type of semaphorins and plexin-neuropilin complexes are high-affinity receptors for this type of semaphorins, whereas plexins alone can bind membrane-bound type of semaphorins (He & Tessier-Lavigne 1997; Tamagnone et al. 1999; Dickson 2002).
Semaphorins mainly function as chemorepellents to guide axons and plexins mediate or transduce repulsive actions of semaphorins, while it is unidentified what receptors mediate attractive actions of semaphorins (Driessens et al. 2001; Swiercz et al. 2002). Tamagnone et al. (1999) showed plexin-B1 as a receptor for a transmembrane semaphorin, Sema4D. We have demonstrated that Sema4D binds to plexin-B2 as well as to plexin-B1. Embryonic DRGs express mRNAs of Sema4D as well as mRNAs of plexin-B1 and B2, and these proteins are localized in the axonal processes of DRG neurones. These results suggest that embryonic DRG neurones could respond to Sema4D in an autocrine or paracrine manner via plexin-B1 and/or plexin-B2. This is the first paper suggesting plexins as the receptors for attractive action of semaphorins.
Plexin-B1 interacts with GTP-Rac1 to inhibit p21-activated kinase (PAK) activation, and it results in inhibition of extension (Driessens et al. 2001). Sema4D has been reported to induce growth cone collapse in the hippocampal culture, via PDZ-RhoGEF which is activator that promotes the conversion of the inactive GDP-bound to the active GTP-bound (Swiercz et al. 2002). PDZ-RhoGEF can associate at the PDZ domain with C-terminus of plexin-B1 (Hirotani et al. 2002), and contains RGS (regulating G-protein signalling) domain, which can be regulated by heterotrimeric G-proteins. Thus Sema4D-plexin-B1 signalling might be modified by heterotrimeric G-protein-coupled receptors (GPCR) through such PDZ-RhoGEFs to convert repellent to attractant and vice versa, although it remains to be studied furthermore.
Association of plexin-B1 with tyrosine kinase type-receptors
Recently, plexin-B1 is reported to couple with tyrosine kinase type-receptor, Met, which is well known as a receptor for hepatocyte growth factor (HGF)/scatter factor receptor (Giordano et al. 2002). Sema4D can stimulate tyrosine kinase activity of Met in the absence of HGF, and that results in invasive growth of epithelial cells. Recently, Morroti et al. (2002) reported that K252a can block tyrosine kinase activity of Met as well as Trks. K252a markedly inhibited Sema4D-axonal outgrowing-action of DRG neurones. It is uncertain which tyrosine kinase receptors, Trk or Met, is involved in the Sema4D-signalling. The skin that is one of target tissues of sensory neurones starts to produce NGF at E11, and the maximum level of NGF is found during E13-15 when plexin-B1 and B2 are expressed in DRGs (Davies et al. 1987). Sema4D likely cooperates with NGF to enhance axonal outgrowth of DRG neurones at this stage.
Our results could suggest that neurite-outgrowing action of Sema4D be likely induced by the interaction of signalling pathways of Sema4D-plexin and tyrosine kinase-type of receptors such as TrkA. The cellular environment of DRG neurones including cAMP/cGMP levels can switch repulsive signals to attractive signals, although it remains to be studied furthermore.
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Experimental procedures |
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Extracellular domain of mouse Sema4D was subcloned into expression vectors of AP-tag1 (Cheng & Flanagan 1994) to express alkaline phosphatase (AP)-fused Sema4D protein (Sema4D- alkaline phosphatase) in HEK293 cells as described (Fujioka et al. 2003). The concentration of Sema4D-AP was determined from AP activity at 405 nm as previously described (Sakai et al. 1999). For the control experiments, the conditioned medium from HEK293 cells (CM) was used instead of the medium from HEK293 cells expressing Sema4D-AP (Sema4D-medium). Sema4D-AP was used for neurite outgrowth assay at 1 nM in this study, with or without 50 ng/mL NGF (7S, Roche Molecular Biochemicals). HEK293 cells were maintained in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% foetal bovine serum (FBS).
DRG neurone culture
DRGs were dissected under a microscope from 10 mice at embryonic day 12.5 (E12.5). About a hundred ganglia were treated with 0.25% trypsin/0.2% EDTA/phosphate-buffered saline (PBS) at 37 °C for 10 min. Dissociated DRG cells were cultured in 5% horse serum/DMEM at 1 x 105 cells/35 mm dish, which was coated with 0.5% polyethylenimine. After 1 h, the culture medium was replaced with the CM or the Sema4D-medium containing 1 nM Sema4D-AP.
Axonal outgrowth assay
DRG neurones were incubated with CM or Sema4D-medium in the absence or presence of 50 ng/mL NGF at 37 °C for 14–20 h. Axonal outgrowth was quantified by measuring the length of the longest neurite of DRG neurones using an eyepiece micrometer. At least three independent experiments were done. All values are given as means ± SEM and statistical significance of any effect was tested with Student's t-test. Difference was considered significant if P < 0.01. K252a (Calbiochem) was used at 100 nM that inhibits autophosphorylation of Trks but does not inhibit EGF- nor bFGF- receptors (Hashimoto 1988; Berg et al. 1992). Anti-NGF polyclonal rabbit antiserum (Sigma) was used at dilutions of 1 : 100 000–1 : 1000 to block endogenous NGF in DRG neurone cultures.
Construction of expression vectors
The cDNAs of human plexin-B1 (KIAA0407) and plexin-B2 (KIAA0315) provided by T. Nagase were subcloned into the expression vectors, pEF-HA and the cytoplasmic domains of human plexin-B1 (plexin-B1cd) and plexin-B2 (plexin-B2cd) was subcloned, respectively, into pCMV-Myc expression vector as described (Hirotani et al. 2002). Expression vectors encoding rat neuropilin-1 (pMT21-rNP1) and mouse neuropilin-2 (pSecTag-mNP2-myc) were provided by Dr M. Tessier-Lavigne (He & Tessier-Lavigne 1997). Extracellular domain of Sema4D (Sema4Ded) was subcloned into pEF-Fc vector (Suda & Nagata 1994).
Preparation of polyclonal antibodies to Sema4D, plexin-B1- and plexin-B2-transfectants
Rabbit polyclonal anti-Sema4D antibodies against Sema4Ded-Fc (Fc-fused-Sema4Ded) and against the cytoplasmic domain of Sema4D (Sema4Dcd) as described (Fujioka et al. 2003; Furuyama et al. 1996). The preimmune IgGs and anti-Sema4D IgGs were obtained from immunoglobulin fractions of the preimmune rabbit-serum and anti-Sema4D antiserum using protein A-Sepharose, respectively. Rabbit polyclonal anti-plexin-B1 and anti-plexin-B2 antibodies were raised against GST-plexin-B1cd and plexin-B2cd, respectively (Hirotani et al. 2002). The antiserum was affinity-purified with each GST-fusion protein covalently coupled to NHS-activated Sepharose (Amersham Pharmacia). The specificity of the antibodies was confirmed by immunoblot analysis using HEK293 cells transfected with the pCMV-Myc-plexin-B1cd and pCMV-Myc-plexin-B2cd, respectively.
Binding assay
HEK293 cells plated in 24-well plates at 5 x 103 cells/well were transfected with expression vectors encoding neuropilin-1, neuropilin-2, plexin-B1 and plexin-B2 by the calcium-phosphate-precipitation method and processed for the binding assay by Cheng & Flanagan (1994) as described (Miyazaki et al. 1999a). In brief, these cells were incubated with the indicated concentrations of Sema4D-AP for 1 h at 37 °C. After fixation in 3% paraformaldehyde-fixative, AP activity was detected by reacting for 2 h at room temperature with nitroblue tetrazolium chloride (NBT) and 5-bromo-4-chloro-3-indolyl phosphate p-toluidine salt (BCIP).
In situ hybridization histochemistry and immunohistochemistry
Embryos at E12.5-day and 14.5-day were fixed with 4% paraformaldehyde, frozen rapidly and cut into parasagittal and coronal sections of 15 µm thickness on a cryostat. The sections were processed for in situ hybridization histochemistry with anti-sense and sense RNA probes labelled with [35S]-UTP as previously described (Inagaki et al. 1995; Furuyama et al. 1996; Miyazaki et al. 1999b). For immunostaining, anti-Sema4D, anti-plexin-B1, and anti-plexin-B2 polyclonal antibodies against each corresponding cytoplasmic-domain, were used in conjunction with the VECSTAIN ABC kit (Vector) as previously described (Inagaki et al. 1991).
Reverse transcriptase polymerase chain reaction (RT-PCR)
RT-PCR experiments with specific primers of mouse plexin-B1 (ATCCACATCTGGAAGACC and GACCTTGTTTTCCACAGC), plexin-B2 (GGAAGAGCCAGCAGGC and TCAGAGGTCTGTAACCTTATT), and CD72 (GAAGACTGTGAAGCAGAG and GCTTGTCAACCTCTGGTC) were performed using cDNA prepared from each mouse tissue and PC12 cells as template (Sambrook et al. 1989). PCR was performed using the Taq DNA polymerase (Sigma) under the following conditions: denaturation at 94 °C for 5 min, 30 cycles at 94 °C for 30 s, 60–64 °C (varied by used primer sets) for 30 s, and 72 °C for 1 min. Aliquots (20 µL) of PCR products were analysed by 1.2% agarose gel as previously described (Hirotani et al. 2002).
Preparation of crude membrane fractions of plexin-B1 and plexin-B2 transfectants
CHO cells transfected with pEF-HA-plexin-B1 and pEF-HA-plexin-B2 were lysed in lysis buffer (20 mM Tris-HCl pH 7.5/1 mM EDTA/150 mM NaCl/0.5% TritonX-100/1 mM PMSF). Each sample was kept on ice for 30 min and centrifuged at 1000 g for 5 min. The supernatant was centrifuged at 10 000 g for 30 min, then the pellet was suspended in 2% CHAPS (Dotite, Japan). The suspension was dialysed against DMEM and used as crude membrane fractions of plexin-B1 and plexin-B2.
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Acknowledgements |
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Footnotes |
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* Correspondence: E-mail: inagaki{at}sahs.med.osaka-u.ac.jp
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References |
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Berg, M.M., Sternberg, D., Parada, L.F. & Chao, M.V. (1992) K-252a inhibits nerve growth factor-induced trk proto-oncogene tyrosine phosphorylation and kinase activity. J. Biol. Chem. 267, 13–16.
Cheng, H.J. & Flanagan, J.G. (1994) Identification and cloning of ELF-1, a developmentally expressed ligand for the Mek and Sek receptor tyrosine kinases. Cell 79, 157–168.[CrossRef][Medline]
Davies, A.M., Bandtlow, C., Heumann, R., et al. (1987) Timing and site of nerve growth factor synthesis in developing skin in relation to innervation and expression of the receptor. Nature 326, 353–358.[CrossRef][Medline]
Delaire, S., Billard, C., Tordjman, R., et al. (2001) Biological activity of soluble CD100. II. Soluble CD100, similarly to H-SemaIII, inhibits immune cell migration. J. Immunol. 166, 4348–4354.
Dickson, B.J. (2002) Molecular mechanisms of axon guidance. Science 298, 1959–1964.
Driessens, M.H., Hu, H., Nobes, C.D., Korsching, S., Rohrer, H. & Thoenen, H. (2001) Plexin-B semaphorin receptors interact directly with active Rac and regulate the actin cytoskeleton by activating Rho. Curr. Biol. 11, 339–344.[CrossRef][Medline]
Fujioka, S., Masuda, K., Toguchi, M., et al. (2003) Neurotrophic effect of semaphorin 4D in PC12 cells. Biochem. Biophys. Res. Commun. 301, 304–310.[CrossRef][Medline]
Fujisawa, H. & Kitsukawa, T. (1998) Receptors for collapsin/semaphorins. Curr. Opin. Neurobiol. 8, 587–592.[CrossRef][Medline]
Furuyama, T., Inagaki, S., Kosugi, A., et al. (1996) Identification of a novel transmembrane semaphorin expressed on lymphocytes. J. Biol. Chem. 272, 23515–23520.
Giordano, S., Corso, S., Conrotto, P., et al. (2002) The semaphorin 4D receptor controls invasive growth by coupling with Met. Nature Cell Biol. 4, 720–724.[CrossRef][Medline]
Hall, K.T., Boumsel, L., Schultze, J.L., et al. (1996) Human CD100, a novel leukocyte semaphorin that promotes B-cell aggregation and differentiation. Proc. Natl. Acad. Sci. USA 93, 11780–11785.
Hashimoto, S. (1988) K-252a, a potent protein kinase inhibitor, blocks nerve growth factor-induced neurite outgrowth and changes in the phosphorylation of proteins in PC12h cells. J. Cell Biol. 107, 1531–1539.
He, Z. & Tessier-Lavigne, M. (1997) Neuropilin is a receptor for the axonal chemorepellent Semaphorin III. Cell 90, 739–751.[CrossRef][Medline]
Hirotani, M., Ohoka, Y., Yamamoto, T., et al. (2002) Interaction of plexin-B1 with PDZ. domain-containing Rho guanine nucleotide exchange factors. Biochem. Biophys. Res. Commun. 297, 32–37.[CrossRef][Medline]
Inagaki, S., Furuyama, T. & Iwahashi, Y. (1995) Identification of a member of mouse semaphorin family. FEBS Lett. 370, 269–272.[CrossRef][Medline]
Inagaki, S., Takagi, H., Suzuki, K., Akai, F. & Taniguchi, N. (1991) Intense immunoreactivity for Mn-superoxide dismutase (Mn-SOD) in cholinergic and non-cholinergic neurons in the rat basal forebrain. Brain Res. 541, 354–357.[CrossRef][Medline]
Kolodkin, A.L., Matthes, D.J. & Goodman, C.S. (1993) The semaphorin genes encode a family of transmembrane and secreted growth cone guidance molecules. Cell 75, 1389–1399.[CrossRef][Medline]
Kumanogoh, A., Watanabe, C., Lee, I., et al. (2000) Identification of CD72 as a lymphocyte receptor for the class IV semaphorin CD100: a novel mechanism for regulating B cell signaling. Immunity 13, 621–631.[CrossRef][Medline]
Luo, Y., Raible, D. & Raper, J.A. (1993) Collapsin, a protein in brain that induces the collapse and paralysis of neuronal growth cones. Cell 75, 217–227.[CrossRef][Medline]
Matsuoka, I., Meyer, M. & Thoenen, H. (1991) Cell-type-specific regulation of nerve growth factor (NGF) synthesis in non-neuronal cells: comparison of Schwann cells with other cell types. J. Neurosci. 11, 3165–3177.[Abstract]
Messersmith, E.K., Leonardo, E.D., Shatz, C.J., Tessier-Lavigne, M., Goodman, C.S. & Kolodkin, A.L. (1995) Semaphorin III can function as a selective chemorepellent to pattern sensory projections in the spinal cord. Neuron 14, 949–959.[CrossRef][Medline]
Miyazaki, N., Furuyama, T., Amasaki, M., et al. (1999a) Mouse semaphorin H inhibits neurite outgrowth from sensory neurons. Neurosci. Res. 33, 269–274.[CrossRef][Medline]
Miyazaki, N., Furuyama, T., Sakai, T., et al. (1999b) Developmental localization of semaphorin H messenger RNA acting as a collapsing factor on sensory axons in the mouse brain. Neuroscience 93, 401–408.[CrossRef][Medline]
Morroti, A., Mila, S., Accornero, P., Tagliabue, E. & Ponzetto, C. (2002) K252a inhibits the oncogenic properties of Met, the HGF receptor. Oncogene 21, 4885–4893.[CrossRef][Medline]
Mueller, B.K. (1999) Growth cone guidance: first step towards a deeper understanding. Annu. Rev. Neurosci. 22, 106–116.
Polleux, F., Morrow, T. & Ghosh, A. (2000) Semaphorin 3A is a chemoattractant for cortical apical dendrites. Nature 404, 567–573.[CrossRef][Medline]
Sakai, T., Furuyama, T., Ohoka, Y., et al. (1999) Mouse semaphorin H induces PC12 cell neurite outgrowth activating Ras-mitogen-activated protein kinase signaling pathway via Ca2+ influx. J. Biol. Chem. 274, 29666–29671.
Sambrook, J., Fritsch, E.F. & Maniatis, T. (1989) Molecular Cloning: a Laboratory Manual, 2nd edn. Cold Spring Harbor, NY: Cold Springer Harbor Laboratory Press.
Semaphorin Nomenclature Committee (1999) Unified nomenclature for the semaphorins/collapsins. Cell 97, 551–552.[CrossRef][Medline]
Shewan, D., Dwivedy, A., Anderson, R. & Holt, C.E. (2002) Age-related changes underlie switch in netrin-1 responsiveness as growth cones advance along visual pathway. Nature Neurosci. 5, 955–961.[CrossRef][Medline]
Song, H.J. & Poo, M.M. (1999) Signal transduction underlying growth cone guidance by diffusible factors. Curr. Opin. Neurobiol. 9, 355–364.[CrossRef][Medline]
Suda, T. & Nagata, S. (1994) Purification and characterization of the Fas-ligand that induces apoptosis. J. Exp. Med. 179, 873–879.
Swiercz, J.M., Kuner, R., Behrens, J. & Offermanns, S. (2002) Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology. Neuron 35, 51–63.[CrossRef][Medline]
Tamagnone, L., Artigiani, S., Chen, H., et al. (1999) Plexins are a large family of receptors for transmembrane, secreted, and GPI-anchored semaphorins in vertebrates. Cell 99, 71–80.[CrossRef][Medline]
Taniguchi, M., Yuasa, S., Fujisawa, H., et al. (1997) Disruption of semaphorin III/D gene causes severe abnormality in peripheral nerve projection. Neuron 19, 519–530.[CrossRef][Medline]
Tessier-Lavigne, M. & Goodman, C.S. (1996) The molecular biology of axon guidance. Science 274, 1123–1133.
Wong, J.T., Wong, S.T. & O'Connor, T.P. (1999) Ectopic semaphorin-1a functions as an attractive guidance cue for developing peripheral neurons. Nature Neurosci. 2, 798–803.[CrossRef][Medline]
Received: 22 March 2004
Accepted: 7 June 2004
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