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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oligodendrocytes develop in defined CNS regions as progenitor cells, which migrate to their final destinations, encountering soluble and membrane-bound signals that influence their differentiation and potential to myelinate axonal projections. To identify the regulatory genes that may be involved in this process, microarray analysis of developing oligodendroglia was performed. Several neural guidance genes, including members of the neuropilin (NP) and semaphorin families were detected. These findings were verified and expanded upon using RT-PCR with RNA from fluorescent activated cell sorted A2B5+ oligodendrocyte progenitors and O4+ pro-oligodendrocytes isolated from in vitro and in vivo sources. RT-PCR, western and immunocytochemical analyses revealed that oligodendrocytes expressed NP1, several alternatively spliced isoforms of NP2, and a broad spectrum of both soluble (Class 3), membrane-spanning (Class 4-6), and membrane-tethered (Class 7) semaphorin ligands. Class 3 semaphorins, in a modified stripe assay, caused the collapse of oligodendrocyte progenitor growth cones, redirection of processes, and altered progenitor migration. Our data support a role for neuropilins and semaphorins in orchestrating the migration patterns of developing oligodendrocytes in the CNS.
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PMID:A role for semaphorins and neuropilins in oligodendrocyte guidance. 1275 85

Peripheral nerve growth is regulated by the coordinated action of numerous external stimuli, including positively acting neurotrophin-derived growth cues and restrictive semaphorin cues. Here, we show that Semaphorin 3F (Sema 3F) can antagonize nerve growth factor (NGF)-stimulated TrkA (tyrosine receptor kinase A) signaling in sympathetic neurons, thereby apparently contributing to growth cone collapse. Sema 3F suppressed NGF-induced activation of the phosphatidylinositol 3 (PI3)-kinase-Akt and MEK (mitogen-activated protein kinase kinase)-ERK (extracellular signal-regulated kinase) pathways, both of which we show to be required to maintain growth cone structure. Sema 3F-induced growth cone collapse was partially reversed by sustained activation of the PI3-kinase and MEK pathways, which was achieved by overexpression of the Gab-1 (growth-associated binder 1) docking protein. These data indicate that a novel mechanism used by Sema 3F to collapse growth cones in sympathetic neurons is to dampen neurotrophin signaling, providing an intracellular mechanism for cross talk between positive and negative axon growth cues.
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PMID:Semaphorin 3F antagonizes neurotrophin-induced phosphatidylinositol 3-kinase and mitogen-activated protein kinase kinase signaling: a mechanism for growth cone collapse. 1293 Jul 99

A new semaphorin inhibitor xanthofulvin was isolated from the cultured broth of a fungus Penicillium sp. SPF-3059 along with a known compound vinaxanthone by solvent extraction and bioassay-guided fractionation. The tautomeric structure of xanthofulvin was determined by spectroscopic analyses. The two compounds exhibited significant semaphorin inhibitory activity with IC50 values of 0.09 and 0.1 microg/ml, respectively, in semaphorin3A-induced growth cone collapse assay using cultured chick dorsal root ganglia neurons.
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PMID:Xanthofulvin, a novel semaphorin inhibitor produced by a strain of Penicillium. 1451 3

Semaphorins (sema) constitute a family of molecules sharing a common extracellular domain (semaphorin domain). This family includes several types of secreted and membrane-associated molecules that are grouped into eight subclasses (subclasses 1-7 and viral semaphorins). Subclass 3 semaphorins are secreted molecules involved in axonal guidance, mainly through repulsive gradients and induction of growth cone collapse. More recently sema 3 molecules have been identified as positive factors in dependence of the type of neurons. Besides their axonal guidance function, some semaphorins have been implicated in apoptosis and survival. We investigated the effect of sema3C on survival and neurite outgrowth of rat cerebellar granule neurons (CGNs) in culture. 3T3 cells were stably transfected with sema3C. Several clonal lines were established and tested for their neuritogenic activity and one, S3C-8, was selected for the bulk of experiments. S3C-8 was co-cultured with CGNs. Sema3C enhanced CGN viability as assessed in co-cultures of CGNs with monolayers of S3C-8 in comparison with co-cultures of CGNs with control mock-transfected 3T3 cells. Moreover sema3C induced neuritogenesis of cultured CGNs, which express neuropilin-1 and -2. S3C-8 cells, overexpressing sema3C, were significantly more neuritogenic for CGN than poly l-lysine (PLL), a positive substrate for CGNs, as assessed by the measurement of the length of neurites and confirmed by Tau expression along the time of culture. CGNs co-cultured with S3C-8, showed up-regulation of the expression of axonal microtubule-associated proteins (MAPs) such as Tau, phosphorylated MAP2C and mode I-phosphorylated MAP1B compared with neurons cultured on control 3T3 cells. We also found increased expression of a specific marker of neuronal cell bodies and dendrites, high molecular weight MAP2 (HMW-MAP2). Interestingly, there was no accompanying up-regulation of a marker enriched within the neuronal somatodendritic domain, mode II-phosphorylated MAP1B. These data support the idea that secreted sema3C favors survival and neuritogenesis of cultured CGNs.
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PMID:Semaphorin 3C preserves survival and induces neuritogenesis of cerebellar granule neurons in culture. 1462 19

An inappropriate cross talk between activated T lymphocytes infiltrating the CNS and neural cells can sustain the onset and progression of demyelination and axonal degeneration in neuroinflammatory diseases. To mimic this deleterious cross talk, we designed an experimental paradigm consisting of transient cocultures of T lymphocytes chronically activated by retrovirus infection (not virus productive) with human multipotent neural precursors or primary oligodendrocytes from rat brain. We showed that activated T lymphocytes induced apoptotic death of multipotent neural progenitors and immature oligodendrocytes after a progressive collapse of their process extensions. These effects were reminiscent of those induced by brain semaphorin on neural cells. Blockade by specific Abs of soluble CD100 (sCD100)/semaphorin 4D released by activated T cells, or treatment with rsCD100, demonstrated that this immune semaphorin has the ability to collapse oligodendrocyte process extensions and to trigger neural cell apoptosis, most likely through receptors of the plexin family. The specific presence of sCD100 in the cerebrospinal fluid and of CD100-expressing T lymphocytes in the spinal cord of patients suffering with neuroinflammatory demyelination pointed to the potential pathological effect of sCD100 in the CNS. Thus, our results show that CD100 is a new important element in the deleterious T cell-neural cell cross talk during neuroinflammation and suggest its role in demyelination or absence of remyelination in neuroinflammatory diseases including multiple sclerosis and human T lymphotropic virus type 1-associated myelopathy.
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PMID:Semaphorin CD100 from activated T lymphocytes induces process extension collapse in oligodendrocytes and death of immature neural cells. 1470 3

The pattern of sensory neuron extensions and connections is established during embryonic development through complex and varied guidance cues that control motility of growth cones and neurite morphogenesis. Semaphorins and neurotrophins are molecules that act as such cues. Collapsin response mediator proteins (CRMPs) are thought to be part of the semaphorin signal transduction pathway implicated in semaphorin-induced growth cone collapse. In this report, we present evidence that CRMPs are also involved in the neurite extension controlled by neurotrophins. We found that specific antibodies and the dominant-negative mutant protein for CRMP2 both potentiated the neurite extension induced by NGF, while specific antibodies and the corresponding mutant protein for CRMP1 both abolished the neurite extension induced by NT3. Our data suggest that CRMP2 has a negative effect on neurite extension induced by NGF and CRMP1 participates in the neurite formation/extension induced by NT3. These results point to a function for CRMPs in the regulation of neurite outgrowth induced by neurotrophins in sensory neurons.
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PMID:Involvement of collapsin response mediator proteins in the neurite extension induced by neurotrophins in dorsal root ganglion neurons. 1503 71

The functional properties and anatomical organization of the mammalian visual cortex are immature at birth and develop gradually during the first postnatal weeks. There is a 'critical period' where the cortex is plastic and susceptible to changes in visual input. Knowledge of proteins with a high expression during this period has great importance for the understanding of activity-driven maturation of the brain. The collapsin response mediator protein family consists of five cytosolic phosphoproteins (CRMP1-5) that are involved in neuronal differentiation during the development of the nervous system. They have been implicated in axon guidance and growth cone collapse through their action in the signalling pathway of collapsin/semaphorin. We examined the distribution of the CRMPs throughout the visual cortex of kitten and adult cat by in situ hybridization. While CRMP3 could not be detected in cat forebrain, the other CRMPs showed a higher expression in the immature brain compared to the adult state. Western blotting allowed the quantification of the observed age-dependent differences in the expression of CRMP2, 4 and 5. Moreover, for CRMP2 and 5 we observed a number of development-dependent post-translational modifications. We thus conclude that CRMPs might be important during the normal postnatal development of the visual cortex possibly for the fine-tuning of the specific connections in the brain.
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PMID:Age-dependent expression of collapsin response mediator proteins (CRMPs) in cat visual cortex. 1509 61

In the mammalian CNS, glial cells repel axons during development and inhibit axon regeneration after injury. It is unknown whether the same repulsive axon guidance molecules expressed by glia and their precursors during development also play a role in inhibiting regeneration in the injured CNS. Here we investigate whether optic nerve glial cells express semaphorin family members and, if so, whether these semaphorins inhibit axon growth by retinal ganglion cells (RGCs). We show that each optic nerve glial cell type, astrocytes, oligodendrocytes, and their precursor cells, expressed a distinct complement of semaphorins. One of these, sema5A, was expressed only by purified oligodendrocytes and their precursors, but not by astrocytes, and was present in both normal and axotomized optic nerve but not in peripheral nerves. Sema5A induced collapse of RGC growth cones and inhibited RGC axon growth when presented as a substrate in vitro. To determine whether sema5A might contribute to inhibition of axon growth after injury, we studied the ability of RGCs to extend axons when cultured on postnatal day (P) 4, P8, and adult optic nerve explants and found that axon growth was strongly inhibited. Blocking sema5A using a neutralizing antibody significantly increased RGC axon growth on these optic nerve explants. These data support the hypothesis that sema5A expression by oligodendrocyte lineage cells contributes to the glial cues that inhibit CNS regeneration.
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PMID:An oligodendrocyte lineage-specific semaphorin, Sema5A, inhibits axon growth by retinal ganglion cells. 1516 91

Plexins constitute a large family of transmembrane proteins that act as receptors for the semaphorin family of ligands. They are best known for their role in growth cone guidance, although they also are widely expressed outside the nervous system. Plexins are thought to control axon guidance by modifying the growth cone cytoskeleton, and Rho GTPases have been strongly implicated in this response. However, the exact contribution of Rho proteins is unclear. Sema3A/Plexin-A1-induced growth cone collapse, for example, requires Rac activity, which is a surprising result given that this GTPase is usually associated with membrane protrusions. We show here that Sema3A-induced collapse of COS-7 cells expressing Plexin-A1 also requires Rac but not Rho activity and that the cytoplasmic tail of Plexin-A1 interacts directly with activated Rac. However, collapse induced by a constitutively activated version of Plexin-A1 does not require Rac. We propose a novel function for Rac, namely that it acts upstream of Plexin-A1 during semaphoring-induced collapse, to regulate the activity of the receptor.
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PMID:The activity of the plexin-A1 receptor is regulated by Rac. 1518 88

Plexins are cell surface receptors for semaphorin molecules, and their interaction governs cell adhesion and migration in a variety of tissues. We report that the Semaphorin 4D (Sema4D) receptor Plexin-B1 directly stimulates the intrinsic guanosine triphosphatase (GTPase) activity of R-Ras, a member of the Ras superfamily of small GTP-binding proteins that has been implicated in promoting cell adhesion and neurite outgrowth. This activity required the interaction of Plexin-B1 with Rnd1, a small GTP-binding protein of the Rho family. Down-regulation of R-Ras activity by the Plexin-B1-Rnd1 complex was essential for the Sema4D-induced growth cone collapse in hippocampal neurons. Thus, Plexin-B1 mediates Sema4D-induced repulsive axon guidance signaling by acting as a GTPase activating protein for R-Ras.
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PMID:The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. 1529 73


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