CYTOPLASMIC DYNEIN STRUCTURE AND FUNCTION

细胞内核迁移在真核生物中起着重要作用 发展。因为核迁移到菌丝体中尤其是 在真菌中很明显，是真菌生长和发育所必需的， 以丝状真菌Nidulans Aspergillusnidulans为模型系统 识别与核迁移有关的分子。一组温度 鉴定出敏感的NUD(核分布)突变体 细胞内的核迁移是有缺陷的。其中两个变种人，裸体 和nudG，编码分子马达的组件，细胞质动力蛋白 分别是重链和轻链。这证明了细胞质动力蛋白 作为核迁徙的主要马达。 初步工作将细胞质动力蛋白定位于植物生长的顶端 菌丝体，并提出了确定这是否为 实际上移动细胞核的动力蛋白。另外两个nod基因nudF和nudF NudC是独一无二的，因为它们编码的蛋白质不是 要么是动力蛋白要么是它的动力蛋白激活剂。NudF编码WD40蛋白 类似于异源三聚体G蛋白的β-亚基。其中包括 蛋白质家族，它最接近(42%的同源性)一个基因，Lis- 1，这在患有无脑畸形的患者中是有缺陷的，这种疾病 大脑不能正常发育。NudC对动力蛋白功能的调节 通过转录后控制nudF蛋白水平间接实现 在牢房里。其他NUD突变仍有待鉴定。这笔赠款 包括识别其他基因的计划，这些基因是 通过识别新的迁移对核迁移具有重要意义 缺陷菌株；通过对几个基因外抑制物的分析 NUD突变；并通过对动力蛋白功能的生化分析 突变菌株。

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.