High CRMP2 expression in peripheral T lymphocytes is associated with recruitment to the brain during virus-induced neuroinflammation

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.
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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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    • "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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