INVOLVEMENT OF DIFFERENT RAB GTPASES IN THE TRAFFICKING OF CXCR4 AND CCR5 HOMO- AND HETERODIMERS BETWEEN THE ENDOPLASMIC RETICULUM AND PLASMA MEMBRANE IN HEK293 AND JURKAT CELLS

Abstract

Little is known about the outward trafficking of receptor dimers from the endoplasmic reticulum to the plasma membrane, or the role that trafficking plays in assembly, targeting and specificity of receptor signalling. Bimolecular fluorescence complementation was used to follow prescribed receptor homo/heterodimers in Jurkat cells and clarify the trafficking itineraries those receptors follow to reach the plasma membrane. Chemokine receptors CXCR4 and CCR5 were chosen due to their implication in numerous pathologies including, HIV and cancer, and their ability to form homo and hetero-oligomers. This study demonstrates that although the individual receptors composing heterodimeric complexes are the same as in homodimeric complexes, the heterodimer traffics and signals independently of its constituent homodimers. The presence of CD4 affects the trafficking of CCR5 containing dimers but not the CXCR4 homodimer. These observations demonstrate the importance of considering receptor heterodimers as distinct signalling entities that should be more carefully and individually characterized.