C-X-C chemokine receptor type 4 – Filamin A complex (CXCR4-FLNA complex)

The C-X-C chemokine receptor type 4 – Filamin A (CXCR4-FLNA) complex is a specialized signaling assembly formed by the physical interaction between the G protein-coupled receptor CXCR4 and the large actin-binding scaffold protein Filamin A (UniProt P61073; UniProt P21333). This complex is primarily localized at the plasma membrane, where FLNA binds to the cytoplasmic C-terminal tail of CXCR4 to facilitate the coupling of extracellular signals to the actin cytoskeleton (Jimenez-Baranda et al., 2007). The primary biological function of this complex is to mediate directed cell migration (chemotaxis) in response to the chemokine CXCL12, a process essential for immune cell trafficking and organogenesis (Gomez-Mouton et al., 2015). In pathological states, the CXCR4-FLNA complex is frequently hijacked; it plays a critical role in cancer metastasis by enabling tumor cells to invade tissues and is also a necessary component for HIV-1 entry and infection of T-cells (Cooper et al., 2011). Drugs such as Plerixafor target the CXCR4 component of this complex to disrupt signaling, effectively inhibiting the downstream cytoskeletal rearrangements required for cell movement (Sun et al., 2010). Consequently, this complex represents a significant therapeutic target for preventing tumor spread and managing hematopoietic stem cell mobilization.

Other names

CXCR4-Filamin A interactionCXCR4-FLNA signaling complexCD184-FLNA complex

Antagonism of the CXCR4 receptor to prevent CXCL12-induced signaling and recruitment of Filamin A, thereby inhibiting cytoskeletal rearrangement and cell motility.