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学术报告:Mechanical force triggers transmembrane signaling by inducing lipid phase separation
时间:2018-04-03 浏览次数:

报告时间201845(周四) 10:00开始

报告地点:生命科学技术学院(东11楼)二楼大会议室

报告人:  娄继忠 研究员(中国科学院生物物理研究所)

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报告内容摘要:

All cells are subjected to mechanical force, and force may regulate a variety of cellular and molecular functions. We use T cells as model system to study the impact for mechanical force at molecular or cellular level. T cells rely upon specific recognition between T-cell receptor (TCR) and peptide conjugated major histocompatibility molecule (pMHC) on an antigen-presenting cell to trigger activation signals. The TCR complex is composed of an αβ heterodimer and the non-covalently associated CD3 signaling components (CD3εγ, CD3εδ, CD3ζζ). The juxtaposition of the squat and rigid heterodimeric CD3 structures on short stalks that flank the taller αβ heterodimer, which tethered to the T cell membrane by long linkers, suggested a TCR-based signal transduction mechanism initiated by mechanical triggering upon antigen recognition in the extracellular domains. Moreover, T-cell signals take “two-signal” format. Besides the signals mediated by the TCR/pMHC interactions, both stimulatory and inhibitory secondary signals exist. These costimulatory and coinhibitory pathways have broader biological functions. The molecules involved in the costimulatory pathways include CD28 and ICOS. CTLA-4 and PD-1 involved in the coinhibitory pathways. Molecular architecture (long extracellular stalk) indicated that PD-1 signal transduction should also be force dependent. Our studies suggest possible molecular mechanism on TCR and PD-1 signal transduction, where mechanical forces trigger the phase separation of membrane lipids, which facilitate the downstream signaling cascade. We proposed that the transmembrane signaling for a class of receptors is mediated by mechanical force, especially the ones with single transmembrane domain and long stalk sequence in the extracellular region. Force may play roles at different levels in activate these receptors for their signal initiation and transmission.

 

报告人简介:

娄继忠,研究员、博士生导师,现任职于中国科学院生物物理研究所。中国科学院百人计划获得者,中科院生物物理所,中国科学院核酸生物学重点实验室,创新课题组组长。

主要研究方向:利用单分子生物物理学和分子动力学模拟方法研究生物大分子动态识别特性。目前的研究工作主要集中在以下两方面

1:以T-细胞为对象研究信号和物质跨膜转运与传导过程的分子机制以及其中的力学调控:(1T细胞受体抗原识别以及抗原结合后信号向细胞内传递的过程;(2PD-1配体识别过程与调控,共抑制信号传递激励。

2IICRISPR-Cas系统靶DNA识别机制。