CXCL12-induced partitioning of flotillin-1 with lipid rafts plays a role in CXCR4 function

Banabihari Giri, Vishwa D. Dixit, Manik C. Ghosh, Gary D. Collins, Islam U. Khan, Karen Madara, Ashani T. Weeraratna, Dennis D. Taub

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Lipid rafts play an important role in signal integration and in the cellular activation of a number of cytokine and growth factor receptors. It has recently been demonstrated that flotillin proteins are recruited to lipid raft microdomains upon cellular activation and play a role in neural cell regeneration, receptor signaling and lymphocyte activation. However, little is known about the relevance of the flotillin proteins during T cell responses to chemoattractant stimulation. To this end, cytoplasmic and lipid raft fractions from human T cells were analyzed for flotillin protein redistribution prior to and after CXCL12 stimulation. Flotillin-1, but not flotillin-2, redistributes to lipid rafts upon CXCR4 ligation. Moreover, in CXCL12-treated T cells, flotillin-1 also associates with several raft proteins including LAT, CD48 and CD11a but not Lck. In addition, an increase in CXCR4 association with flotillin-1 in lipid rafts was observed after chemokine treatment. RNAi technology was also utilized to inhibit the expression of flotillin-1, resulting in an inhibition of CXCL12-mediated signaling, function and CXCR4 recruitment into lipid rafts. Together, these data suggest that the increased association of cellular flotillin-1 with lipid raft microdomains during chemokine exposure may play an important role in chemokine receptor signaling and receptor partitioning with lipid rafts.

Original languageEnglish (US)
Pages (from-to)2104-2116
Number of pages13
JournalEuropean Journal of Immunology
Volume37
Issue number8
DOIs
StatePublished - Aug 1 2007
Externally publishedYes

Keywords

  • CXCL12
  • CXCR4
  • Chemotaxis
  • Flotillin-1
  • Lipid rafts

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Giri, B., Dixit, V. D., Ghosh, M. C., Collins, G. D., Khan, I. U., Madara, K., Weeraratna, A. T., & Taub, D. D. (2007). CXCL12-induced partitioning of flotillin-1 with lipid rafts plays a role in CXCR4 function. European Journal of Immunology, 37(8), 2104-2116. https://doi.org/10.1002/eji.200636680