High CRMP2 expression in peripheral T lymphocytes is associated with recruitment to the

Inserm, U842, Lyon, F-69372 France.
Journal of Neuroimmunology (Impact Factor: 2.47). 02/2008; 193(1-2):38-51. DOI: 10.1016/j.jneuroim.2007.09.033
Source: PubMed


Collapsin Response Mediator Protein (CRMP)-2 is involved in T-cell polarization and migration. To address the role of CRMP2 in neuroinflammation, we analyzed its involvement in lymphocyte recruitment to the central nervous system in mouse infected with neurotropic and non-neurotropic virus strains (RABV, CDV). A sub-population of early-activated CD69+CD3+ T lymphocytes highly expressing CRMP2 (CRMP2hi) peaked in the blood, lymph nodes and brain of mice infected with neurotropic viruses, and correlated with severity of disease. They displayed high migratory properties reduced by CRMP2 blocking antibody. These data point out the potential use of CRMP2 as a peripheral indicator of neuroinflammation.

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    • "Proteins such as B-cell differentiation antigen CD72 (CD72), which is related to B-cell proliferation and differentiation, Ig heavy chain V region AC38 205.12, with antigen binding function, and killer cell lectin-like receptor, subfamily A, member 4 (Klra4), involved with innate immunity and cell adhesion as a receptor on natural killer (NK) cells for class I MHC, were all found in CRMP2 interactome (table 1). Although there are no previous reports linking CRMP2 and such proteins, CRMP2 was highly expressed in peripheral T cells during virus-induced neuroinflammation [69] and may regulate T cell migration [70] [71]. Moreover, the semaphoring interactions detected in CRMP2 interactome may suggest the participation of CRMP2 in the regulation of the immune system mediated by neuropilin 1 (NRP1) and plexins [72]. "
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    ABSTRACT: Collapsin response mediator protein-2 (CRMP2) is a central nervous system protein involved in neuronal development, axonal and neuronal growth, cell migration, and protein trafficking. Recent studies have linked perturbations in CRMP2 function to neurodegenerative disorders such as Alzheimer's disease, neuropathic pain and Batten disease, and to psychiatric disorders such as schizophrenia. Like most proteins, CRMP2 functions though interactions with a molecular network of proteins and other molecules. Here, we have attempted to identify additional proteins of the CRMP2 interactome to provide further leads about its roles in neurological functions. We used a combined co-immunoprecipitation and shotgun proteomic approach in order to identify CRMP2 protein partners. We identified 78 CRMP2 protein partners not previously reported in public protein interaction databases. These were involved in 7 biological processes, which included cell signaling, growth, metabolism, trafficking and immune function, according to Gene Ontology classifications. Furthermore, 32 different molecular functions were found to be associated with these proteins, such as RNA binding, ribosomal functions, transporter activity, receptor activity, serine/threonine phosphatase activity, cell adhesion, cytoskeletal protein binding and catalytic activity. In silico pathway interactome construction revealed a highly connected network with the most overrepresented functions corresponding to semaphorin interactions, along with axon guidance and WNT5A-signalling. Taken together, these findings suggest that the CRMP2 pathway is critical for regulating neuronal and synaptic architecture. Further studies along these lines might uncover novel biomarkers and drug targets for use in drug discovery. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    PROTEOMICS - CLINICAL APPLICATIONS 04/2015; 9(9). DOI:10.1002/prca.201500004 · 2.96 Impact Factor
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    • "This is likely not the case because after infection with an encephalitic RABV strain, blood T-cells expressed markers of activation (CD69) and were highly positive for collapsing response mediator protein 2 (CRMP2), a marker of T-cell polarization and migration. The brain was enriched with this type of cells, indicating they have migratory properties (Vuaillat et al., 2008). Thus, activation and entry into the NS are not limiting factors for T-cell protective function. "
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    ABSTRACT: Rabies virus (RABV) is a strictly neurotropic virus that slowly propagates in the nervous system (NS) of the infected host from the site of entry (usually due to a bite) up to the site of exit (salivary glands). Successful achievement of the virus cycle relies on the preservation of the neuronal network. Once RABV has entered the NS, its progression is not interrupted either by destruction of the infected neurons or by the immune response, which are major host mechanisms for combating viral infection. RABV has developed two main mechanisms to escape the host defenses: (1) its ability to kill protective migrating T cells and (2) its ability to sneak into the NS without triggering apoptosis of the infected neurons and preserving the integrity of neurites.
    Advances in Virus Research 01/2011; 79:33-53. DOI:10.1016/B978-0-12-387040-7.00003-2 · 4.57 Impact Factor
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    • "In agreement with a previous report (Ying et al. 2003b), BMP4 strongly inhibited early neural differentiation as shown by reduced expression of Sox1 and nestin (Supplemental Fig. S10). Dpysl2, also known as Crmp2, has been implicated to function in axon guidance and in neural diseases such as Alzheimer's disease, neuroinflammation, and schizophrenia (Zhao et al. 2006; Cole et al. 2007; Vuaillat et al. 2008). As the Dpysl2 promoter is co-occupied by both SMAD1/5 and SMAD4 (Figs. 1C, 2B) and its expression is attenuated by BMP4 in day 8 EB (Fig. 3C), we explored its function in BMP-regulated early neural differentiation . "
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    ABSTRACT: Embryonic stem (ES) cells are under precise control of both intrinsic self-renewal gene regulatory network and extrinsic growth factor-triggered signaling cascades. How external signaling pathways connect to core self-renewal transcriptional circuits is largely unknown. To probe this, we chose BMP signaling, which is previously recognized as a master control for both self-renewal and lineage commitment of murine ES cells. Here, we mapped target gene promoter occupancy of SMAD1/5 and SMAD4 on a genome-wide scale and found that they associate with a large group of developmental regulators that are enriched for H3K27 trimethylation and H3K4 trimethylation bivalent marks and are repressed in the self-renewing state, whereas they are rapidly induced upon differentiation. Smad knockdown experiments further indicate that SMAD-mediated BMP signaling is largely required for differentiation-related processes rather than directly influencing self-renewal. Among the SMAD-associated genes, we further identified Dpysl2 (previously known as Crmp2) and the H3K27 demethylase Kdm6b (previously known as Jmjd3) as BMP4-modulated early neural differentiation regulators. Combined with computational analysis, our results suggest that SMAD-mediated BMP signaling balances self-renewal versus differentiation by modulating a set of developmental regulators.
    Genome Research 11/2009; 20(1):36-44. DOI:10.1101/gr.092114.109 · 14.63 Impact Factor
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