CXCR5 overexpression in HL-60 cells enhances chemotaxis toward CXCL13 without anticipated interaction partners or enhanced MAPK signaling.
CXCR5 overexpression in HL-60 cells enhances chemotaxis toward CXCL13 without anticipated interaction partners or enhanced MAPK signaling.
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DOI：
10.1007/s11626-018-0293-z
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Yen A
中科院分区：
文献类型：
--
作者：
MacDonald RJ;Yen A
CXCR 5是一种蛇形受体，参与淋巴细胞的细胞迁移和白细胞的分化。它导致MAPK通路活化，并具有已知的信号传导膜伴侣。据报道，CXCR 5 mRNA在分离后在中性粒细胞中表达，但其在该细胞环境中的作用尚不清楚。CXCR 5也在HL-60细胞（一种人急性髓性白血病细胞系）中表达，在用全反式视黄酸处理后，其诱导向嗜中性粒细胞样状态分化。CXCR 5是这个过程所必需的;分化在CXCR 5敲除的细胞中受损，在异位表达的细胞中增强。由于CXCR 5具有各种膜蛋白伴侣，我们研究了CXCR 5驱动的全反式维甲酸诱导的分化是否依赖于其与这些伴侣的关联。为了实现这一点，我们产生了过表达该蛋白的HL-60细胞。我们发现，CXCR 5驱动迁移向其配体，CXCL 13，并探测与几个候选人使用流式细胞术为基础的福斯特共振能量转移的相互作用。令人惊讶的是，我们没有检测到与任何候选人的相互作用，包括在其他细胞环境中报告的三种。此外，我们没有观察到全反式维甲酸诱导的分化的显着变化，这可能是由于CXCR 5和伴侣受体或CXCL 13的化学计量。令人惊讶的是，预期的膜伴侣对于下游CXCR 5信号传导和全反式视黄酸诱导的分化显然是不必要的。
CXCR5 is a serpentine receptor implicated in cell migration in lymphocytes and differentiation in leukocytes. It causes MAPK pathway activation and has known membrane partners for signaling. CXCR5 mRNA is reportedly expressed in neutrophils following isolation, but its role in this cellular context is unknown. CXCR5 is also expressed in HL-60 cells, a human acute myeloid leukemia line, following treatment with all-trans retinoic acid, which induces differentiation toward a neutrophil-like state. CXCR5 is necessary for this process; differentiation was crippled in CXCR5 knockout cells and enhanced in cells ectopically expressing it. Since CXCR5 has various membrane protein partners, we investigated whether CXCR5-driven all-trans retinoic acid-induced differentiation depends on its association with such partners. Pursuing this, we generated HL-60 cells overexpressing the protein. We found that CXCR5 drove migration toward its ligand, CXCL13, and probed for interactions with several candidates using flow cytometry-based Förster resonance energy transfer. Surprisingly, we did not detect interactions with any candidates, including three reported in other cellular contexts. Additionally, we observed no significant changes in all-trans retinoic acid-induced differentiation; this may be due to the stoichiometry of CXCR5 and partner receptors or CXCL13. The anticipated membrane partnerings were surprisingly apparently unnecessary for downstream CXCR5 signaling and all-trans retinoic acid-induced differentiation.
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影响因子：
3.7
作者：
Bunaciu RP;Jensen HA;MacDonald RJ;LaTocha DH;Varner JD;Yen A
通讯作者：
Yen A
影响因子：
11.4
作者：
通讯作者：
--
影响因子：
3.6
作者：
Ebert, LA;Schaerli, P;Moser, B
通讯作者：
Moser, B
影响因子：
4
作者：
Lamkin, TJ;Chin, V;Yen, A
通讯作者：
Yen, A
DOI：
10.1073/pnas.77.5.2936
发表时间：
1980-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
BREITMAN, TR;SELONICK, SE;COLLINS, SJ
通讯作者：
COLLINS, SJ