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

Vuaillat, Carine; Varrin‐Doyer, Michel; Bernard, Arlette; Sagardoy, I.; Cavagna, Sylvie; Chounlamountri, I.; Lafon, Monique; Giraudon, Pascale

doi:10.1016/j.jneuroim.2007.09.033

Cited by 33 publications

(25 citation statements)

References 71 publications

(64 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Differential phosphorylation by glycogen synthase kinase3b and Yes was supposed to modulate the contribution of CRMP2 to cytoskeletal reorganization during chemokine-induced T cell migration (25). In addition, we showed that in mouse models of virus-induced neuroinflammation, the elevated CRMP2 expression in blood lymphocytes correlated with CNS infiltration and clinical signs, suggesting the potential use of CRMP2 as a peripheral indicator of neuroinflammation (26). Extending our analysis to human, we detected high CRMP2 expression in T lymphocytes of HTLV-1-infected patients suffering from neurologic disease compared with asymptomatic virus carriers (24).…”

mentioning

confidence: 80%

Human T Lymphotropic Virus Type 1 Increases T Lymphocyte Migration by Recruiting the Cytoskeleton Organizer CRMP2

Varrin‐Doyer

Nicolle

Marignier

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

Recruitment of virus-infected T lymphocytes into the CNS is an essential step in the development of virus-associated neuroinflammatory diseases, notably myelopathy induced by retrovirus human T leukemia virus-1 (HTLV-1). We have recently shown the key role of collapsin response mediator protein 2 (CRMP2), a phosphoprotein involved in cytoskeleton rearrangement, in the control of human lymphocyte migration and in brain targeting in animal models of virus-induced neuroinflammation. Using lymphocytes cloned from infected patients and chronically infected T cells, we found that HTLV-1 affects CRMP2 activity, resulting in an increased migratory potential. Elevated CRMP2 expression accompanies a higher phosphorylation level of CRMP2 and its more pronounced adhesion to tubulin and actin. CRMP2 forms, a full length and a shorter, cleaved one, are also affected. Tax transfection and extinction strategies show the involvement of this viral protein in enhanced full-length and active CRMP2, resulting in prominent migratory rate. A role for other viral proteins in CRMP2 phosphorylation is suspected. Full-length CRMP2 confers a migratory advantage possibly by preempting the negative effect of short CRMP2 we observe on T lymphocyte migration. In addition, HTLV-1–induced migration seems, in part, supported by the ability of infected cell to increase the proteosomal degradation of short CRMP2. Finally, gene expression in CD69+ cells selected from patients suggests that HTLV-1 has the capacity to influence the CRMP2/PI3K/Akt axis thus to positively control cytoskeleton organization and lymphocyte migration. Our data provide an additional clue to understanding the infiltration of HTLV-1–infected lymphocytes into various tissues and suggest that the regulation of CRMP2 activity by virus infection is a novel aspect of neuroinflammation.

show abstract

mentioning

confidence: 80%

Human T Lymphotropic Virus Type 1 Increases T Lymphocyte Migration by Recruiting the Cytoskeleton Organizer CRMP2

Varrin‐Doyer

Nicolle

Marignier

et al. 2012

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…As a protein interacting partner of tubulin, actin, and vimentin, CRMP2 participates in processes that regulate cytoskeletal dynamics and the balance between neurite collapse and outgrowth. [13][14][15] Proximity of CRMP2 to cytoskeletal proteins and the cell membrane led to the discovery of additional functions in cellular trafficking. [16][17][18][19][20][21] Our laboratory has further expanded this role by demonstrating that CRMP2 mediates trafficking of N-type voltage-gated calcium (CaV2.2) channels.…”

Section: Introductionmentioning

confidence: 99%

A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function

et al. 2017

View full text Add to dashboard Cite

The neuronal collapsin response mediator protein 2 (CRMP2) undergoes several posttranslational modifications that codify its functions. Most recently, CRMP2 SUMOylation (addition of small ubiquitin like modifier (SUMO)) was identified as a key regulatory step within a modification program that codes for CRMP2 interaction with, and trafficking of, voltage-gated sodium channel NaV1.7. In this paper, we illustrate the utility of combining sequence alignment within protein families with structural analysis to identify, from several putative SUMOylation sites, those that are most likely to be biologically relevant. Co-opting this principle to CRMP2, we demonstrate that, of 3 sites predicted to be SUMOylated in CRMP2, only the lysine 374 site is a SUMOylation client. A reduction in NaV1.7 currents was the corollary of the loss of CRMP2 SUMOylation at this site. A 1.78-A -resolution crystal structure of mouse CRMP2 was solved using X-ray crystallography, revealing lysine 374 as buried within the CRMP2 tetramer interface but exposed in the monomer. Since CRMP2 SUMOylation is dependent on phosphorylation, we postulate that this state forces CRMP2 toward a monomer, exposing the SUMO site and consequently, resulting in constitutive regulation of NaV1.7.

show abstract

“…Prominent infiltration of activated lymphocytes and dendritic cells with high CRMP2 levels was observed in the CNS of mice infected either with paramyxovirus CDV or rabies virus. 50 This correlated the degrees of clinical manifestation. By extrapolation, one can suppose that chronic activation of the CRMP2-associated signaling pathway by a virus could amplify immune cell motility and subsequent neuroinvasion.…”

Section: Discussionmentioning

confidence: 88%

Insight into the role of CRMP2 (collapsin response mediator protein 2) in T lymphocyte migration

Giraudon

Nicolle

Cavagna

et al. 2013

Cell Adhesion & Migration

View full text Add to dashboard Cite

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

Cited by 33 publications

References 71 publications

Human T Lymphotropic Virus Type 1 Increases T Lymphocyte Migration by Recruiting the Cytoskeleton Organizer CRMP2

Human T Lymphotropic Virus Type 1 Increases T Lymphocyte Migration by Recruiting the Cytoskeleton Organizer CRMP2

A single structurally conserved SUMOylation site in CRMP2 controls NaV1.7 function

Insight into the role of CRMP2 (collapsin response mediator protein 2) in T lymphocyte migration

Contact Info

Product

Resources

About