The LIS1-related Protein NUDF of Aspergillus nidulans and Its Interaction Partner NUDE Bind Directly to Specific Subunits of Dynein and Dynactin and to α- and γ-Tubulin

Abstract

The NUDF protein of Aspergillus nidulans, which is required for nuclear migration through the fungal mycelium, closely resembles the LIS1 protein required for migration of neurons to the cerebral cortex in humans. Genetic experiments suggested that NUDF influences nuclear migration by affecting cytoplasmic dynein. NUDF interacts with another protein, NUDE, which also affects nuclear migration in A. nidulans. Interactions among LIS1, NUDE, dynein, and ␥-tubulin have been demonstrated in animal cells. In this paper we examine the interactions of the A. nidulans NUDF and NUDE proteins with components of dynein, dynactin, and with ␣-and ␥-tubulin. We show that NUDF binds directly to ␣-and ␥-tubulin and to the first P-loop of the cytoplasmic dynein heavy chain, whereas NUDE binds directly to ␣-and ␥-tubulin, to NUDK (actin-related protein 1), and to the NUDG dynein LC8 light chain. The data suggest a direct role for NUDF in regulation of the dynein heavy chain and an effect on other dynein/dynactin subunits via NUDE. The interactions between NUDE, NUDF, and ␥-tubulin suggest that this protein may also be involved in the regulation of dynein function. Additive interactions between NUDE and dynein and dynactin subunits suggest that NUDE acts as a scaffolding factor between components.

LIS1, CLIP-170's Key to the Dynein/Dynactin Pathway

“…nudF, a LIS1 homolog in the fungus Aspergillus nidulans, was identified in a screen for mutants defective in nuclear migration (46,82). Genetic and biochemical evidence suggested that nudF regulates dynein motor activity and MT dynamics (3,29,31,(79)(80)(81). These findings are consistent with interaction of mammalian LIS1 with tubulin (58) and are corroborated by its interaction with the first P-loop of dynein heavy chain (60).…”

Lessons from the Genome Sequence ofNeurospora crassa: Tracing the Path from Genomic Blueprint to Multicellular Organism

“…Interestingly, this type of Rho protein is especially important for the growth and development of polarity in neuronal cells and may play a similar role in the filamentous fungi. Although the suggestion that the hyphal cell is a simpler version of a neuron may seem far-fetched, several examples from the area of motor proteins and organelle transport support this view (343,421,538,700,831). Interestingly, several potential Rac homologs are present in the dimorphic fungus Yarrowia lipoytica (357).…”

Poliovirus Protein 3A Binds and Deregulates LIS1, Causing Block of Membrane Protein Trafficking and Deregulation of Cell Division

“…LIS1, encoded by the gene the mutation in which is associated with the type I lissencephaly, 16,17 has been defined as a major cellular interactor of 3A. LIS1 was previously shown to be involved in the dynein motor complex that determines microtubule-associated movement of organelles and membrane vesicles [18][19][20][21][22][23][24][25][26] and maintenance of the integrity of the Golgi apparatus and juxta-centrosomal distribution of its membranes (reviewed in refs. [27][28][29][30][31][32][33][34][35].…”