Jan 10, 2016

CXCR4 signaling is controlled by immobilization at the plasma membrane

Biochimica Et Biophysica Acta
Elena BeletkaiaThomas Schmidt

Abstract

Understanding of the regulation mechanisms of CXCR4 signaling is essential for revealing its role in physiological and pathological processes. Though biochemical pathways following CXCR4 activation by its ligand CXCL12 are well established, knowledge about the receptor dynamics on the plasma membrane remains limited. Here we used Ewing sarcoma-derived cells to unravel the processes that are involved in regulating CXCR4 dynamics on the plasma membrane during receptor signaling. Single-molecule epi-fluorescence microscopy showed that CXCR4 was present in monomeric state on the plasma membrane independent of receptor stimulation. However, upon activation freely diffusing receptors were immobilized in a ligand concentration-dependent manner. CXCR4 immobilization was strongly correlated with the ability for G-protein signaling and was a precursor of subsequent endocytotic events. Our data suggest that, a balanced regulation of G-protein dependent and independent pathways is required for controlling CXCR4 receptor mobility, and potentially subsequent controlled signal transduction.

  • References51
  • Citations3

Mentioned in this Paper

Guanosine
Biochemical Pathway
Stromal Cell-Derived Factor 1
G-Protein Signaling Pathway
Endocytosis
CXCR4 gene
Regulation of Biological Process
CXCL12 gene
Early Endosome
C-X-C Motif Chemokine 12 Receptor Activity

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