The Rap GTPases Regulate B Cell Migration Toward the Chemokine Stromal Cell-Derived Factor-1 (CXCL12): Potential Role for Rap2 in Promoting B Cell Migration

Abstract

Stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant for B cells and B cell progenitors. Although the binding of SDF-1 to its receptor, CXCR4, activates multiple signaling pathways, the mechanism by which SDF-1 regulates cell migration is not completely understood. In this report we show that activation of the Rap GTPases is important for B cells to migrate toward SDF-1. We found that treating B cells with SDF-1 resulted in the rapid activation of both Rap1 and Rap2. Moreover, blocking the activation of Rap1 and Rap2 via the expression of a Rap-specific GTPase-activating protein significantly reduced the ability of B cells to migrate toward SDF-1. Conversely, expressing a constitutively active form of Rap2 increased SDF-1-induced B cell migration. Thus, the Rap GTPases control cellular processes that are important for B cells to migrate toward SDF-1.

Focal adhesion kinase is required for CXCL12-induced chemotactic and pro-adhesive responses in hematopoietic precursor cells

“…39,40 We thus tested whether silencing of FAK affects CXCL12-induced Rap1 activation. In agreement with previous reports on CXCL12-induced Rap1 activation in hematopoietic cells, 40,41 we show that CXCL12 induced Rap1 activation in CTR-RNAi cells (Figure 3d) and in intact REH cells (not shown).…”

Anatomical Society Summer Meeting in Galway

“…Rap1 is known to stimulate integrin activation, cytoskeleton rearrangements, and cell polarization both in the presence and absence of a chemokine gradient. 42,43 We observed that Rap1a and Rap1b depletion abolished the migratory advantage of MEC1-CD38H cells. This indicates that Rap1 activity contributes to the increased migration and adhesion linked to CD38 expression.…”

Expression of chemokines and gelatinase B in sympathetic ophthalmia

“…30 SDF-1 is a chemokine that plays an important role in B-cell development, trafficking, and activation. [8][9][10][11] Several studies suggested that SDF-1 may have a crucial role in the development of autoimmune disease. Matin et al 31 demonstrated that the chemokine SDF-1 may be an essential chemoattractant in trafficking and migration of mature autoreactive B cells from bone marrow to the periphery or inflammatory sites in the development of autoimmune diabetes.…”

“…8 It is a chemoattractant for monocytes, naive and memory T lymphocytes, and B lymphocytes. [9][10][11] SDF-1 is also a costimulatory factor for CD4 þ T-lymphocyte activation. 12 In view of the presence of an important mononuclear cell infiltrate in SO, MCP-1 and SDF-1 are candidate chemokines for investigation.…”