PDF(Pubmed)
Abstract：
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.
摘要：
CXCR4基因杂合子常染色体显性突变引起WHIM综合征,严重的联合免疫缺陷疾病。突变主要影响CXCR4趋化因子受体的C末端区域，特别是对激动剂（CXCL12）介导的受体内化和脱敏至关重要的几个潜在磷酸化位点。突变受体在细胞表面的停留时间延长，导致过度活跃的信号，这是WHIM综合征的一些症状的原因。最近的研究表明，情况比最初想象的要复杂，由于突变WHIM受体和CXCR4在细胞膜上表现出不同的动力学，这也影响了它们各自的细胞功能。这篇综述探讨了CXCR4的功能机制以及WHIM突变在生理和病理条件下的影响。
