The Organization and Function of the Toxoplasma Daughter Cell Scaffold

弓形虫子细胞支架的组织和功能

• 批准号: 10083185
• 负责人: Ira J Blader
• 金额: $ 66.08万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-01-08 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10083185
• 关键词: 3-Dimensional; Antiparasitic Agents; Apical; Cell Maturation; Cell Nucleus; Cell membrane; Cells; Centrosome; Complex; Cullin Proteins; Cytokinesis; Data; Daughter; Defect; Development; Disease; F Box Domain; F-Box Proteins; Fetal Development; Future; Growth; Guanosine Triphosphate Phosphohydrolases; Immunocompromised Host; Interphase; Life; Membrane; Microscopy; Modeling; Mothers; Names; Organelles; Parasites; Plasmodium; Process; Proteins; Proteomics; Publishing; Research; Resolution; Role; Skeleton; Structure; Testing; Toxoplasma; Trimethoprim-Sulfamethoxazole; Work; base; cell motility; daughter cell; new therapeutic target; novel; oligomycin sensitivity-conferring protein; pathogen; protein complex; receptor; recruit; scaffold; screening; ubiquitin-protein ligase

Uncontrolled Toxoplasma growth is the primary mechanism by which the parasite causes severe and life-threatening disease. The parasite replicates by a process termed endodyogeny, where two daughter parasites form within a single mother. A key step in endodyogeny is formation of the daughter cell inner membrane complex, which is an unique organelle that lies directly underneath the plasma membrane and is required for parasite motility and replication. During daughter cell development, the nascent IMC emerges from a complex named the daughter cell scaffold (DCS). Despite its importance, the DCS is poorly characterized and few of its constituent proteins are known. Here, we hypothesize that the Toxoplasma F-box protein, TgFBXO1, is a critical component of the DCS. To test our hypothesis, we will determine: i) how TgFBXO1 is targeted to the DCS, ii) how TgFBXO1 regulates inner membrane complex development and organization, and iii) which TgFBXO1-interacting proteins are important for inner membrane complex development. Together, these studies will provide in depth mechanistic detail for a protein complex that is critical for growth of an important protozoan pathogen. Furthermore, they were serve as a springboard for future studies aimed at developing novel anti-parasitic drugs that function by targeting this complex.

不受控制的弓形虫生长是该寄生虫致病的主要机制