title: CYFIP2 is highly abundant in CD4+ cells from multiple sclerosis patients and is involved in T cell adhesion.
abstract: DNA microarray profiling of CD4(+) and CD8(+) cells from non-treated relapsing and remitting multiple sclerosis (MS) patients determined that the cytoplasmic binding partner of fragile X protein (CYFIP2, also called PIR121) was increased significantly compared to healthy controls. Western analysis confirmed that CYFIP2 protein was increased approximately fourfold in CD4(+) cells from MS compared to inflammatory bowel disorder (IBD) patients or healthy controls. Because CYFIP2 acts as part of a tetrameric complex that regulates WAVE1 activation we hypothesized that high levels of CYFIP2 facilitate T cell adhesion, which is elevated in MS patients. Several findings indicated that increased levels of CYFIP2 facilitated adhesion. First, adenoviral-mediated overexpression of CYFIP2 in Jurkat cells increased fibronectin-mediated adhesion. Secondly, CYFIP2 knock-down experiments using antisense oligodeoxynucleotides reduced fibronectin-mediated binding in Jurkat and CD4(+) cells. Thirdly, inhibition of Rac-1, a physical partner with CYFIP2 and regulator of WAVE1 activity, reduced fibronectin-mediated adhesion in Jurkat and CD4(+) cells. Finally, inhibition of Rac-1 or reduction of CYFIP2 protein decreased fibronectin-mediated adhesion in CD4(+) cells from MS patients to levels similar to controls. These studies suggest that overabundance of CYFIP2 protein facilitates increased adhesion properties of T cells from MS patients.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Manitoba, Division of Neuroscience, St. Boniface Hospital Research Centre, Winnipeg, Canada. michael.mayne@nrc.gc.ca
authors.forename: Michael
authors.initials: M
authors.lastname: Mayne
authors.forename: Teri
authors.initials: T
authors.lastname: Moffatt
authors.forename: Hong
authors.initials: H
authors.lastname: Kong
authors.forename: Paul J
authors.initials: PJ
authors.lastname: McLaren
authors.forename: Keith R
authors.initials: KR
authors.lastname: Fowke
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Becker
authors.forename: Mike
authors.initials: M
authors.lastname: Namaka
authors.forename: Annette
authors.initials: A
authors.lastname: Schenck
authors.forename: Barbara
authors.initials: B
authors.lastname: Bardoni
authors.forename: Charles N
authors.initials: CN
authors.lastname: Bernstein
authors.forename: Maria
authors.initials: M
authors.lastname: Melanson
mesh_terms: D000328:Adult; D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D002448:Cell Adhesion / Q000276:immunology; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology; D019169:Jurkat Cells; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002352:Carrier Proteins