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http://purl.uniprot.org/citations/20479866http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/20479866http://www.w3.org/2000/01/rdf-schema#comment"

Background

T cell activation and immune synapse formation require the appropriate activation and clustering of the integrin, LFA-1. Previous work has reported that the calpain family of calcium-dependent proteases are important regulators of integrin activation and modulate T cell adhesion and migration. However, these studies have been limited by the use of calpain inhibitors, which have known off-target effects.

Methodology/principal findings

Here, we used a LoxP/CRE system to specifically deplete calpain 4, a small regulatory calpain subunit required for expression and activity of ubiquitously expressed calpains 1 and 2, in CD4+ T cells. CD4+ and CD8+ T cells developed normally in Capn4(F/F):CD4-CRE mice and had severely diminished expression of Calpain 1 and 2, diminished talin proteolysis and impaired casein degradation. Calpain 4-deficient T cells showed no difference in adhesion or migration on the LFA-1 ligand ICAM-1 compared to control T cells. Moreover, there was no impairment in conjugation between Capn4(F/F):CD4-CRE T cells and antigen presenting cells, and the conjugates were still capable of polarizing LFA-1, PKC-theta and actin to the immune synapse. Furthermore, T cells from Capn4(F/F):CD4-CRE mice showed normal proliferation in response to either anti-CD3/CD28 coated beads or cognate antigen-loaded splenocytes. Finally, there were no differences in the rates of apoptosis following extrinsic and intrinsic apoptotic stimuli.

Conclusion/significance

Our findings demonstrate that calpain 4 is not necessary for LFA-1-mediated adhesion, conjugation or migration. These results challenge previous reports that implicate a central role for calpains in the regulation of T cell LFA-1 function."xsd:string
http://purl.uniprot.org/citations/20479866http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0010513"xsd:string
http://purl.uniprot.org/citations/20479866http://purl.uniprot.org/core/author"Huttenlocher A."xsd:string
http://purl.uniprot.org/citations/20479866http://purl.uniprot.org/core/author"Greer P.A."xsd:string
http://purl.uniprot.org/citations/20479866http://purl.uniprot.org/core/author"Seroogy C.M."xsd:string
http://purl.uniprot.org/citations/20479866http://purl.uniprot.org/core/author"Wernimont S.A."xsd:string
http://purl.uniprot.org/citations/20479866http://purl.uniprot.org/core/author"Simonson W.T."xsd:string
http://purl.uniprot.org/citations/20479866http://purl.uniprot.org/core/date"2010"xsd:gYear
http://purl.uniprot.org/citations/20479866http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/20479866http://purl.uniprot.org/core/pages"e10513"xsd:string
http://purl.uniprot.org/citations/20479866http://purl.uniprot.org/core/title"Calpain 4 is not necessary for LFA-1-mediated function in CD4+ T cells."xsd:string
http://purl.uniprot.org/citations/20479866http://purl.uniprot.org/core/volume"5"xsd:string
http://purl.uniprot.org/citations/20479866http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/20479866
http://purl.uniprot.org/citations/20479866http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/20479866
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http://purl.uniprot.org/uniprot/#_P11835-mappedCitation-20479866http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/20479866
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http://purl.uniprot.org/uniprot/P11835http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/20479866
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