Actin Assembly Regulation in Lytic Synapse Formation

裂解突触形成中的肌动蛋白组装调节

• 批准号: 7529006
• 负责人: William Boyd Butler
• 金额: $ 4.96万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7529006
• 关键词: Actins; Adhesions; Affect; Biological Assay; Biology; Bone Marrow; Cancer Patient; Cell Communication; Cell physiology; Cell surface; Cells; Characteristics; Chromosome Pairing; Clinical Research; Complex; Confocal Microscopy; Cytolysis; Cytoskeleton; EEF1A2 gene; Employee Strikes; Engraftment; Eukaryota; Eukaryotic Cell; Filament; Genetic; Goals; Hematopoietic; Histocompatibility Antigens Class I; Homologous Gene; Immune; Immunotherapy; Ligands; Lipid Bilayers; Localized; Lytic; Medical Surveillance; Microfilaments; Natural Killer Cells; Phosphorylation; Play; Process; Proteins; Regulation; Role; Stimulus; Synapses; System; Tetracycline; Tetracyclines; Total Internal Reflection Fluorescent; YWHAQ gene; cancer cell; clinically relevant; human EMS1 protein; migration; prevent; receptor; research study; response; small hairpin RNA; success; synaptogenesis; tumor

DESCRIPTION (provided by applicant): Regulated actin assembly is a critical component of immune cell function, as genetic and pharmacological inhibition of actin cytoskeletal dynamics renders immune cells incapable of performing many of their effector functions: Actin assembly regulation is a complex process that involves many proteins including actin nucleators as well as their activators and effectors. The exact role and distinct modes of actin nucleation have yet to be elucidated in immune cells and how these processes affect immune cell functions. Activators of actin nucleation including cortactin have been largely studied in cells of non-hematopoietic lineage. However, in cells of hematopoietic lineage, adhesion, migration and actin cytoskeletal dynamics are highly regulated as to prevent unwarranted immune cell functions. Arp2/3 and formins are two distinct actin nucleators and HS1 is a known activator of Arp2/3, yet their roles in immune cell functions and in particular NK cells remains incompletely understood. Clinically, NK cells are capable of promoting bone marrow rejection and as well as engraftment, in addition, Nk cells elicit potent anti-tumor effects. The clinical relevance of NK cells has begun to be appreciated and new clinical studies utilizing NK cells for the treatment of cancer patients have begun to be met with modest success. However with only limited understanding as to how NK cells interact with target cancer cells, it will be difficult to advance NK immunotherapy. Following completion of the experiments in this proposal, there will be greater understanding of the role that regulated actin assembly plays in the ability of NK cells to carry out their functions critical to immune tumor surveillance necessary for the survival of higher eukaryotes.

描述（由申请人提供）：受调节的肌动蛋白组装是免疫细胞功能的关键组成部分，因为遗传和药理抑制肌动蛋白细胞骨架动力学使免疫细胞无法执行其许多效应子功能：肌动蛋白组装调节是一个复杂的过程，它涉及许多蛋白质，涉及许多蛋白质蛋白，包括actin natectors nutepotors nuteTors以及其激活剂以及其激活剂和效应。肌动蛋白成核的确切作用和不同的模式尚未在免疫细胞中阐明，以及这些过程如何影响免疫细胞功能。肌动蛋白成核的活化剂在内，已在非脊髓元谱系细胞中进行了很大的研究。然而，在造血谱系细胞中，粘附，迁移和肌动蛋白细胞骨架动力学受到高度调节，以防止不必要的免疫细胞功能。 ARP2/3和formins是两个不同的肌动蛋白核定剂，HS1是ARP2/3的已知激活剂，但它们在免疫细胞功能中的作用，尤其是NK细胞仍然尚不完全了解。在临床上，NK细胞能够促进骨髓排斥和植入，此外，NK细胞会引起有效的抗肿瘤作用。 NK细胞的临床相关性已开始受到赞赏，利用NK细胞治疗癌症患者的新临床研究已开始获得适度的成功。但是，只有对NK细胞如何与目标癌细胞相互作用的有限理解，将很难推进NK免疫疗法。在本提案中完成实验后，将对调节肌动蛋白组装在NK细胞执行其对免疫肿瘤监测至关重要的功能的能力中发挥作用的作用有更深入的了解。