CYTOPLASMIC DYNEIN STRUCTURE AND FUNCTION

细胞质动力蛋白结构和功能

• 批准号: 2685050
• 负责人: N. R MORRIS
• 金额: $ 30.64万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-04-09 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2685050
• 关键词: Aspergillus; cell nucleus; dynein ATPase; fungal genetics; intracellular transport; protein structure function

Intracellular nuclear migration plays an important role in eukaryotic development. Because nuclear migration into the mycelium is particularly conspicuous in fungi and is required for fungal growth and development, the filamentous fungus Aspergillus nidulans was used as a model system to identify molecules involved in nuclear migration. A set of temperature sensitive nud (nuclear distribution) mutants was identified in which intracellular nuclear migration is defective. Two of these mutants, nudA and nudG, encode components of a molecular motor, the cytoplasmic dynein heavy and light chains respectively. This identified cytoplasmic dynein as the main motor responsible for nuclear migration in A. nidulans. Preliminary work localized cytoplasmic dynein to the growing tip of the mycelium, and plans are presented for determining whether this is the dynein that actually moves the nucleus. Two other nud genes, nudF and nudC, are unique because they encode proteins that are not components of either dynein or its dynactin activator. nudF encodes a WD40 protein similar to the beta-subunit of the heterotrimeric G proteins. Among this family of proteins, it most closely resembles (42% identity) a gene, LIS- 1, that is defective in patients with lissencephaly, a disease in which the brain fails to develop properly. nudC regulates dynein function indirectly by posttranscriptionally controlling the level of nudF protein in the cell. Other nud mutations remain to be characterized. This grant includes plans for the identification of additional genes that are important for nuclear migration by identification of new migration defective strains; by analysis of extragenic suppressors of several of the nud mutations; and by biochemical analyses of dynein function in mutant strains.

细胞内核迁移在真核生物中起着重要的作用 发展因为细胞核向菌丝体的迁移 在真菌中是显著的并且是真菌生长和发育所需的， 丝状真菌构巢曲霉被用作模型系统， 识别参与核迁移的分子。一组温度 鉴定了敏感的nud（核分布）突变体，其中 细胞内核迁移是有缺陷的。其中两个突变体nudA 和nudG，编码分子马达的成分，细胞质动力蛋白 重链和轻链。这一鉴定的细胞质动力蛋白 作为A. nidulans。 初步工作将细胞质动力蛋白定位于生长的尖端， 菌丝体，并提出计划，以确定这是否是 动力蛋白，它能移动细胞核另外两个nud基因nudF和 nudC是独特的，因为它们编码的蛋白质不是 动力蛋白或其动力肌动蛋白激活剂。nudF编码WD 40蛋白 类似于异源三聚体G蛋白的β亚基。这中间 家族的蛋白质，它最接近（42%的同一性）的基因，LIS- 1，即无脑回畸形患者有缺陷， 大脑无法正常发育nudC调节动力蛋白功能 间接通过转录后控制nudF蛋白的水平 在细胞中。其他nud突变仍有待鉴定。这笔赠款 包括鉴定其他基因的计划， 通过识别新迁移对核迁移很重要 缺陷菌株;通过分析几种 nud突变;并通过动力蛋白功能的生化分析， 突变株