PT  - JOURNAL ARTICLE
AU  - Saria Mcheik
AU  - Nils Van Eeckhout
AU  - Cédric De Poorter
AU  - Céline Galés
AU  - Marc Parmentier
AU  - Jean-Yves Springael
TI  - Coexpression of CCR7 and CXCR4 during B cell development controls CXCR4 responsiveness and bone marrow homing
AID  - 10.1101/689372
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 689372
4099  - http://biorxiv.org/content/early/2019/07/02/689372.short
4100  - http://biorxiv.org/content/early/2019/07/02/689372.full
AB  - G protein-coupled receptors (GPCR) constitute the largest family of plasma membrane proteins involved in cell signaling. Besides their canonical role in signaling, GPCR can also act as allosteric modulator of one another through receptor oligomerization. However, only few studies have investigated the relevance of GPCR oligomerization, and the role of GPCR interaction in physiological processes remains largely unknown. By using chemokine receptors and B cell development as a model system, we unveil in this study a novel role for CCR7 as a selective endogenous allosteric modulator of CXCR4. We show that the upregulation of CCR7 expression naturally occurring in late stages of B cell development contributes to the functional inactivation of CXCR4, and that B cell populations from CCR7-/- mice display higher responsiveness to CXCL12 and improved retention in the bone marrow parenchyma. We also provide molecular evidences supporting a model in which upregulation of CCR7 favors the formation of CXCR4-CCR7 heteromers wherein CXCR4 is selectively impaired in its ability to activate some G protein complexes.