Isolation of a new set of Aspergillus nidulans mutants defective in nuclear migration

Xiang, Xin; Zuo, Wenqi; Efimov, Vladimir P.; Morris, Nicholas P.

doi:10.1007/s002940050461

Cited by 81 publications

(73 citation statements)

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“…In addition, nudG encodes a homologue of LC8 (ref. 23), which is one of the nud genes involved in nuclear migration in fungi 24,25 . Indeed, dynein, LIS1, NDEL1 and mammalian NUDC (mNUDC) are all nud genes 25 .…”

Section: Resultsmentioning

confidence: 99%

“…23), which is one of the nud genes involved in nuclear migration in fungi 24,25 . Indeed, dynein, LIS1, NDEL1 and mammalian NUDC (mNUDC) are all nud genes 25 . Therefore, we also examined whether LC8 also stimulates disassembly of dynein-dynactin complex.…”

Section: Resultsmentioning

confidence: 99%

“…23). In the filamentous fungus Aspergillus nidulans, nud mutants have been isolated, including nudA, nudF, nudE, nudG and nudC 24,25 . nudA, nudF and nudE encode dynein HC, LIS1 and NDEL/ NDE1, respectively.…”

Section: Discussionmentioning

confidence: 99%

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Arl3 and LC8 regulate dissociation of dynactin from dynein

et al. 2014

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Cytoplasmic dynein acts as a motor for the intracellular retrograde motility of vesicles and organelles along microtubules. However, the regulatory mechanism underlying release of dynactin bound cargoes from dynein motor remains largely unknown. Here we report that ADP-ribosylation factor-like 3 (Arl3) and dynein light chain LC8 induce dissociation of dynactin from dynein. Immunoprecipitation and microtubule pull-down assays revealed that Arl3(Q71L) and LC8 facilitated detachment of dynactin from dynein. We also demonstrated Arl3(Q71L) or LC8-mediated dynactin release from a dynein-dynactin complex through trace experiments using quantum dot (Qdot)-conjugated proteins. Furthermore, we disclosed interactions of Arl3 and LC8 with dynactin and dynein, respectively, by live-cell imaging. Finally, knockdown (KD) of Arl3 and LC8 by siRNA induced abnormal localizations of dynein, dynactin and related organelles. Our findings uncovered the surprising functional relevance of GTP-bound Arl3 and LC8 for the unloading regulation of dynactin-bound cargo from dynein motor.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Arl3 and LC8 regulate dissociation of dynactin from dynein

et al. 2014

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“…The Aspergillus orthologue of LIS1, NUDF, 145 functions within a complex of NUD proteins, including NUDA (dynein heavy chain), NUDG (dynein light chain), NUDK (dynactin subunit Arp1) and NUDE. [145][146][147][148][149] The composition of this complex is conserved in mammals, demonstrating that nuclear positioning is an indispensable function. Aspergillus NUDE has two mammalian orthologues termed NUDE and NUDE-like (NDE1 and NDEL1), which interact with LIS1.…”

Section: Lis1 Ndel1 Nde1 and Disc1mentioning

confidence: 99%

The DISC locus in psychiatric illness

et al. 2007

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The DISC locus is located at the breakpoint of a balanced t(1;11) chromosomal translocation in a large and unique Scottish family. This translocation segregates in a highly statistically significant manner with a broad diagnosis of psychiatric illness, including schizophrenia, bipolar disorder and major depression, as well as with a narrow diagnosis of schizophrenia alone. Two novel genes were identified at this locus and due to the high prevalence of schizophrenia in this family, they were named Disrupted-in-Schizophrenia-1 (DISC1) and Disrupted-in-Schizophrenia-2 (DISC2). DISC1 encodes a novel multifunctional scaffold protein, whereas DISC2 is a putative noncoding RNA gene antisense to DISC1. A number of independent genetic linkage and association studies in diverse populations support the original linkage findings in the Scottish family and genetic evidence now implicates the DISC locus in susceptibility to schizophrenia, schizoaffective disorder, bipolar disorder and major depression as well as various cognitive traits. Despite this, with the exception of the t(1;11) translocation, robust evidence for a functional variant(s) is still lacking and genetic heterogeneity is likely. Of the two genes identified at this locus, DISC1 has been prioritized as the most probable candidate susceptibility gene for psychiatric illness, as its protein sequence is directly disrupted by the translocation. Much research has been undertaken in recent years to elucidate the biological functions of the DISC1 protein and to further our understanding of how it contributes to the pathogenesis of schizophrenia. These data are the main subject of this review; however, the potential involvement of DISC2 in the pathogenesis of psychiatric illness is also discussed. A detailed picture of DISC1 function is now emerging, which encompasses roles in neurodevelopment, cytoskeletal function and cAMP signalling, and several DISC1 interactors have also been defined as independent genetic susceptibility factors for psychiatric illness. DISC1 is a hub protein in a multidimensional risk pathway for major mental illness, and studies of this pathway are opening up opportunities for a better understanding of causality and possible mechanisms of intervention. Molecular Psychiatry (2008) 13, 36-64; doi:10.1038/sj.mp.4002106; published online 2 October 2007 Keywords: schizophrenia; bipolar disorder; depression; DISC1; DISC2; mouse models Genetics of DISC1 discoverySt Clair et al. 1 first reported a Scottish family with a high loading of major mental illness, which cosegregates with a t(1;11) translocation. Long-term follow-up of this family over a period of 30 years has reported 87 family members, of whom 37 carry the translocation. 2 Of 29 individuals carrying the translocation, for whom psychiatric assessment was possible, 7 have a diagnosis of schizophrenia, 1 has a diagnosis of bipolar disorder and 10 cases of recurrent major depression were also reported. 2 Thus, 18 of 29 translocation carriers are diagnosed with major mental illness whereas none of...

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“…Media, growth conditions, genetic crosses, A. nidulans transformations, and genomic DNA isolation were as described previously (Xiang et al 1995a,b;Willins et al 1995Willins et al , 1997. In many experiments described in this article, we transformed A. nidulans strains in which the A. nidulans Ku70 homolog was deleted (DnkuA) (Nayak et al 2006), with individual genomic fragments plus the plasmid pAid containing the pyrG selective marker (Xiang et al 1999). The DnkuA strains made most of the described experiments feasible due to an increased frequency of homologous integration of a genomic fragment into the A. nidulans genome (Nayak et al 2006).…”

Section: Strains and Aspergillus Techniquesmentioning

confidence: 99%

Point Mutations in the Stem Region and the Fourth AAA Domain of Cytoplasmic Dynein Heavy Chain Partially Suppress the Phenotype of NUDF/LIS1 Loss in Aspergillus nidulans

Zhuang

Zhang²,

Xiang

2007

Genetics

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Cytoplasmic dynein performs multiple cellular tasks but its regulation remains unclear. The dynein heavy chain has a N-terminal stem that binds to other subunits and a C-terminal motor unit that contains six AAA (ATPase associated with cellular activities) domains and a microtubule-binding site located between AAA4 and AAA5. In Aspergillus nidulans, NUDF (a LIS1 homolog) functions in the dynein pathway, and two nudF6 partial suppressors were mapped to the nudA dynein heavy chain locus. Here we identified these two mutations. The nudAL1098F mutation resides in the stem region, and nudAR3086C is in the end of AAA4. These mutations partially suppress the phenotype of nudF deletion but do not suppress the phenotype exhibited by mutants of dynein intermediate chain and Arp1. Surprisingly, the stronger DnudF suppressor, nudAR3086C, causes an obvious decrease in the basal level of dynein's ATPase activity and an increase in dynein's distribution along microtubules. Thus, suppression of the DnudF phenotype may result from mechanisms other than simply the enhancement of dynein's ATPase activity. The fact that a mutation in the end of AAA4 negatively regulates dynein's ATPase activity but partially compensates for NUDF loss indicates the importance of the AAA4 domain in dynein regulation in vivo.

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Isolation of a new set of Aspergillus nidulans mutants defective in nuclear migration

Cited by 81 publications

References 26 publications

Arl3 and LC8 regulate dissociation of dynactin from dynein

Arl3 and LC8 regulate dissociation of dynactin from dynein

The DISC locus in psychiatric illness

Point Mutations in the Stem Region and the Fourth AAA Domain of Cytoplasmic Dynein Heavy Chain Partially Suppress the Phenotype of NUDF/LIS1 Loss in Aspergillus nidulans

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