Fibronectin stimulates TRPV1 translocation in primary sensory neurons.

Fibronectin stimulates TRPV1 translocation in primary sensory neurons.
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纤连蛋白刺激初级感觉神经元中的 TRPV1 易位。

DOI:
10.1111/j.1471-4159.2008.05779.x
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发表时间:
2009-02
影响因子:
4.7
通讯作者:
Milam, Stephen B.
Milam, Stephen B.
中科院分区:
医学2区
文献类型:
--
作者:
Jeske, Nathaniel A.;Patwardhan, Amol M.;Henry, Michael A.;Milam, Stephen B.

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细胞外基质 (ECM) 分子的组成和受体识别差异很大。它们普遍存在的表达谱与细胞生长、分化和存活中的作用有关。最近的工作已经确定了某些 ECM 分子可以作为动态信号调节剂,而不是信号转导的长期调节作用。在这项研究中,我们研究了纤连蛋白在三叉神经节 (TG) 感觉神经元 TRPV1 易位到质膜的动态调节中所起的作用。共聚焦免疫荧光分析鉴定了 TRPV1 受体与结合纤连蛋白的整合素亚基的共表达。用纤连蛋白培养或处理的 TG 神经元在辣椒素刺激的神经肽释放的 EC50 中经历了左移。这种纤连蛋白诱导的 TRPV1 对激活敏感性的增加与 TRPV1 质膜表达的增加以及 TG 神经元中 TRPV1 酪氨酸磷酸化的增加相结合。此外,与在聚-D-赖氨酸上培养的神经元相比,在纤连蛋白上培养的TG神经元表现出辣椒素介导的Ca+2积累的增加。这些研究提供的数据表明,纤连蛋白刺激 TRPV1 受体酪氨酸磷酸化依赖性易位至质膜,从而确定纤连蛋白是能够使感觉神经元敏化的 ECM 的关键成分。
Extracellular matrix (ECM) molecules are highly variable in their composition and receptor recognition. Their ubiquitous expression profile has been linked to roles in cell growth, differentiation, and survival. Recent work has identified certain ECM molecules that serve as dynamic signal modulators, versus the more-recognized role of chronic modulation of signal transduction. In this study, we investigated the role that fibronectin plays in the dynamic modulation of TRPV1 translocation to the plasma membrane in trigeminal ganglia (TG) sensory neurons. Confocal immunofluorescence analyses identify co-expression of the TRPV1 receptor with integrin subunits that bind fibronectin. TG neurons cultured upon or treated with fibronectin experienced a leftward shift in the EC50 of capsaicin-stimulated neuropeptide release. This fibronectin-induced increase in TRPV1 sensitivity to activation is coupled by an increase in plasma membrane expression of TRPV1, as well as an increase in tyrosine phosphorylation of TRPV1 in TG neurons. Furthermore, TG neurons cultured on fibronectin demonstrated an increase in capsaicin-mediated Ca+2 accumulation relative to neurons cultured on poly-D-lysine. Data presented from these studies indicate that fibronectin stimulates tyrosine-phosphorylation-dependent translocation of the TRPV1 receptor to the plasma membrane, identifying fibronectin as a critical component of the ECM capable of sensory neuron sensitization.
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