Vallee, R. B. & Tsai, J. W. The cellular roles of the lissencephaly gene LIS1, and what they tell us about brain development. Genes Dev. 20, 1384-1393

Department of Pathology and Cell Biology, Center for Neurobiology and Behavior, Columbia University College of Physicians and Surgeons, New York, New York 10032 USA.
Genes & Development (Impact Factor: 12.64). 07/2006; 20(11):1384-93. DOI: 10.1101/gad.1417206
Source: PubMed
  • Source
    • "These data imply that KASH5 is an adaptor for cytoplasmic dynein. Additional coIP experiments revealed associations with dynein IC and p150 Glued as well as with LIS1, another dynein regulator (Fig. 2 F; Vallee and Tsai, 2006). We next prepared a series of KASH5 deletion mutants (Fig. 2 E). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chromosome pairing is an essential meiotic event that ensures faithful haploidization and recombination of the genome. Pairing of homologous chromosomes is facilitated by telomere-led chromosome movements and formation of a meiotic bouquet, where telomeres cluster to one pole of the nucleus. In metazoans, telomere clustering is dynein and microtubule dependent and requires Sun1, an inner nuclear membrane protein. Here we provide a functional analysis of KASH5, a mammalian dynein-binding protein of the outer nuclear membrane that forms a meiotic complex with Sun1. This protein is related to zebrafish futile cycle (Fue), a nuclear envelope (NE) constituent required for pronuclear migration. Mice deficient in this Fue homologue are infertile. Males display meiotic arrest in which pairing of homologous chromosomes fails. These findings demonstrate that telomere attachment to the NE is insufficient to promote pairing and that telomere attachment sites must be coupled to cytoplasmic dynein and the microtubule system to ensure meiotic progression.
    The Journal of Cell Biology 09/2013; 202(7). DOI:10.1083/jcb.201304004 · 9.69 Impact Factor
  • Source
    • "Lis1 is widely expressed in postnatal and adult brain, including hippocampus and barrel cortex, and enriched in synaptosomal fractions (McKenney et al, 2010; Niethammer et al, 2000). While the role of Lis1 during neuronal proliferation and migration has been comprehensively studied (Vallee & Tsai, 2006), its role in post-migrational neurons remains largely unknown. Previous electrophysiological study of Lis1 þ/À neurons showed over-excitation of excitatory hippocampal circuits as a consequence of increased presynaptic vesicle numbers per terminal (Greenwood et al, 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: LIS1 (PAFAH1B1) mutation can impair neuronal migration, causing lissencephaly in humans. LIS1 loss is associated with dynein protein motor dysfunction, and disrupts the actin cytoskeleton through disregulated RhoGTPases. Recently, LIS1 was implicated as an important protein-network interaction node with high-risk autism spectrum disorder genes expressed in the synapse. How LIS1 might participate in this disorder has not been investigated. We examined the role of LIS1 in synaptogenesis of post-migrational neurons and social behaviour in mice. Two-photon imaging of actin-rich dendritic filopodia and spines in vivo showed significant reductions in elimination and turnover rates of dendritic protrusions of layer V pyramidal neurons in adolescent Lis1+/- mice. Lis1+/- filopodia on immature hippocampal neurons in vitro exhibited reduced density, length and RhoA dependent impaired dynamics compared to Lis1+/+ . Moreover, Lis1+/- adolescent mice exhibited deficits in social interaction. Lis1 inactivation restricted to the postnatal hippocampus resulted in similar deficits in dendritic protrusion density and social interactions. Thus, LIS1 plays prominently in dendritic filopodia dynamics and spine turnover implicating reduced dendritic spine plasticity as contributing to developmental autistic-like behaviour.
    EMBO Molecular Medicine 04/2013; 5(4). DOI:10.1002/emmm.201202106 · 8.25 Impact Factor
  • Source
    • "Lis1 was later linked to dynein motor function through genetic studies in Aspergillus nidulans, which demonstrated that Lis1/nudF, like dynein/nudA, was required for normal nuclear distribution (Xiang et al., 1995). Lis1's role in the dynein-mediated positioning of nuclei and centrosomes is well documented (Xiang et al., 1995; Faulkner et al., 2000; Dujardin et al., 2003; Lee et al., 2003; Cockell et al., 2004; Tanaka et al., 2004; Levy and Holzbaur, 2006; Vallee and Tsai, 2006; Tsai et al., 2007; Youn et al., 2009), but its role in the transport of other dynein cargos remains less clear. Several studies have shown that reducing Lis1 expression leads to defects in the distribution or transport of endosomes , Golgi, and lysosomes (Liu et al., 2000; Smith et al., 2000; Lenz et al., 2006; Ding et al., 2009; Lam et al., 2010; Zhang et al., 2010; Yi et al., 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The molecular motor cytoplasmic dynein is responsible for most minus-end-directed, microtubule-based transport in eukaryotic cells. It is especially important in neurons, where defects in microtubule-based motility have been linked to neurological diseases. For example, lissencephaly is caused by mutations in the dynein-associated protein Lis1. In this paper, using the long, highly polarized hyphae of the filamentous fungus Aspergillus nidulans, we show that three morphologically and functionally distinct dynein cargos showed transport defects in the genetic absence of Lis1/nudF, raising the possibility that Lis1 is ubiquitously used for dynein-based transport. Surprisingly, both dynein and its cargo moved at normal speeds in the absence of Lis1 but with reduced frequency. Moreover, Lis1, unlike dynein and dynactin, was absent from moving dynein cargos, further suggesting that Lis1 is not required for dynein-based cargo motility once it has commenced. Based on these observations, we propose that Lis1 has a general role in initiating dynein-driven motility.
    The Journal of Cell Biology 06/2012; 197(7):971-82. DOI:10.1083/jcb.201112101 · 9.69 Impact Factor
Show more