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PMID:22623988

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Citation

Christie, DA, Kirchhof, MG, Vardhana, S, Dustin, ML and Madrenas, J (2012) Mitochondrial and plasma membrane pools of stomatin-like protein 2 coalesce at the immunological synapse during T cell activation. PLoS ONE 7:e37144

Abstract

Stomatin-like protein 2 (SLP-2) is a member of the stomatin-prohibitin-flotillin-HflC/K (SPFH) superfamily. Recent evidence indicates that SLP-2 is involved in the organization of cardiolipin-enriched microdomains in mitochondrial membranes and the regulation of mitochondrial biogenesis and function. In T cells, this role translates into enhanced T cell activation. Although the major pool of SLP-2 is associated with mitochondria, we show here that there is an additional pool of SLP-2 associated with the plasma membrane of T cells. Both plasma membrane-associated and mitochondria-associated pools of SLP-2 coalesce at the immunological synapse (IS) upon T cell activation. SLP-2 is not required for formation of IS nor for the re-localization of mitochondria to the IS because SLP-2-deficient T cells showed normal re-localization of these organelles in response to T cell activation. Interestingly, upon T cell activation, we found the surface pool of SLP-2 mostly excluded from the central supramolecular activation complex, and enriched in the peripheral area of the IS where signalling TCR microclusters are located. Based on these results, we propose that SLP-2 facilitates the compartmentalization not only of mitochondrial membranes but also of the plasma membrane into functional microdomains. In this latter location, SLP-2 may facilitate the optimal assembly of TCR signalosome components. Our data also suggest that there may be a net exchange of membrane material between mitochondria and plasma membrane, explaining the presence of some mitochondrial proteins in the plasma membrane.

Links

PubMed PMC3356372 Online version:10.1371/journal.pone.0037144

Keywords

Animals; Blood Proteins/metabolism; Cell Membrane/metabolism; Humans; Immunological Synapses/metabolism; Immunoprecipitation; Jurkat Cells; Lymphocyte Activation/immunology; Membrane Proteins/metabolism; Mice; Microscopy, Confocal; Mitochondria/metabolism; Plasmids/genetics; RNA, Small Interfering/genetics; T-Lymphocytes/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:STML2

located_in

GO:0019897: extrinsic component of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:STML2

located_in

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:STML2

located_in

GO:0019897: extrinsic component of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:STML2

colocalizes_with

GO:0001772: immunological synapse

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:STML2

part_of

GO:0005739: mitochondrion

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:STML2

part_of

GO:0019897: extrinsic component of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:STML2

NOT|involved_in

GO:0051646: mitochondrion localization

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

Notes

See also

References

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