Department of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
Department of Molecular Immunology, Faculty of Biology, Institute of Biology III, University of Freiburg, Freiburg, Germany.
Front Immunol. 2024 Jul 3;15:1440499. doi: 10.3389/fimmu.2024.1440499. eCollection 2024.
The tyrosine kinase Lck is mandatory for initiating signaling responses downstream the antigenic T cell receptor (TCR). Numerous studies have shown that a prerequisite for efficient and well-balanced Lck regulation and function is its finely orchestrated spatial distribution pattern, especially at the plane of the plasma membrane. There is a wealth of knowledge on Lck localization sites, preference for specialized lipid microenvironments and colocalization partners. However, several questions concerning the spatial organization of its differentially phosphorylated conformers and the dynamics of their juxtaposition in relation to ligated and non-ligated TCRs remain elusive. In this brief report we introduce a non-invasive nanobody-based approach for mapping Lck subcellular allocation with high precision. Our initial data using this methodology, provide insight into the topology of Lck in resting T cells and its confined localization in a strictly delimited environment within the plane of the plasma membrane.
酪氨酸激酶 Lck 是启动抗原 T 细胞受体（TCR）下游信号转导反应所必需的。大量研究表明，高效、平衡的 Lck 调节和功能的一个前提条件是其精细协调的空间分布模式，特别是在质膜平面上。关于 Lck 的定位部位、对专门脂质微环境的偏好以及共定位伙伴，已经有了丰富的知识。然而，关于其差异磷酸化构象的空间组织及其与配体和非配体 TCR 相关的并置动力学的几个问题仍然难以捉摸。在本简要报告中，我们介绍了一种非侵入性的纳米体方法，用于高精度绘制 Lck 的亚细胞分配图。我们使用该方法的初步数据提供了关于静止 T 细胞中 Lck 的拓扑结构及其在质膜平面内严格限定环境中的局限定位的深入了解。
