The complex nature of CXCR4 mutations in WHIM syndrome

Heterozygous autosomal dominant mutations in the CXCR4 gene cause WHIM syndrome, a severe combined immunodeficiency disorder. The mutations primarily affect the C-terminal region of the CXCR4 chemokine receptor, specifically several potential phosphorylation sites critical for agonist (CXCL12)-media...

Full description

Saved in:
Bibliographic Details
Published in:Frontiers in immunology 2024-07, Vol.15, p.1406532
Main Authors: Rodríguez-Frade, José Miguel, González-Granado, Luis Ignacio, Santiago, César A, Mellado, Mario
Format: Article
Language:English
Subjects:
Animals
Chemokine CXCL12 - genetics
Chemokine CXCL12 - metabolism
CXCL12
CXCR4
Humans
Mutation
Primary Immunodeficiency Diseases - genetics
receptor conformations
Receptors, CXCR4 - genetics
Receptors, CXCR4 - metabolism
Severe Combined Immunodeficiency - genetics
Severe Combined Immunodeficiency - immunology
Signal Transduction
signaling pathways
Thrombocytopenia - genetics
Warts - genetics
WHIM syndrome
β-arrestins
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Heterozygous autosomal dominant mutations in the CXCR4 gene cause WHIM syndrome, a severe combined immunodeficiency disorder. The mutations primarily affect the C-terminal region of the CXCR4 chemokine receptor, specifically several potential phosphorylation sites critical for agonist (CXCL12)-mediated receptor internalization and desensitization. Mutant receptors have a prolonged residence time on the cell surface, leading to hyperactive signaling that is responsible for some of the symptoms of WHIM syndrome. Recent studies have shown that the situation is more complex than originally thought, as mutant WHIM receptors and CXCR4 exhibit different dynamics at the cell membrane, which also influences their respective cellular functions. This review examines the functional mechanisms of CXCR4 and the impact of WHIM mutations in both physiological and pathological conditions.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2024.1406532