Lissencephaly gene (LIS1) expression in the CNS suggests a role in neuronal migration

Reiner, Orly; Albrecht, Urs; Gordon, Michal; Chianese, KA; Wong, Chen Khuan; Gal-Gerber, O.; Sapir, Tamar; Siracusa, LD; Buchberg, AM; Caskey, C. Thomas

doi:10.1523/jneurosci.15-05-03730.1995

Cited by 114 publications

(77 citation statements)

References 30 publications

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“…LIS1 is a regulatory subunit of platelet-activating factor acetylhydrolase (PAFAH) isoform l␤ (Hattori 1994). The developmental expression pattern of murine Lis1 is consistent with an important role for this gene in early embryonic development and neuronal migration (Reiner et al 1995;Albrecht et al 1996). Lis1 is expressed in all three germ layers and extraembryonic tissue, and in the neuroepithelium of all regions of the central nervous system.…”

Section: Introductionmentioning

confidence: 70%

Impaired Learning and Motor Behavior in Heterozygous Pafah1b1 (Lis1) Mutant Mice

Paylor¹,

Hirotsune²,

Gambello³

et al. 1999

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Section: Introductionmentioning

confidence: 70%

Impaired Learning and Motor Behavior in Heterozygous Pafah1b1 (Lis1) Mutant Mice

Paylor¹,

Hirotsune²,

Gambello³

et al. 1999

Learn. Mem.

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“…In mouse brain Disc1, Ndel1 and Lis1 expression overlaps within the developing cerebral cortex 77,83,152,168,169 and other regions, including the hippocampal dentate gyrus. 55,77,83,168,170 These proteins are all present at the post-synaptic density, 91,150 while Lis1 and DISC1 are also present at additional synaptic locations, 91,171 suggesting roles in synaptic transmission.…”

Section: Lis1 Ndel1 Nde1 and Disc1mentioning

confidence: 99%

“…55,77,83,168,170 These proteins are all present at the post-synaptic density, 91,150 while Lis1 and DISC1 are also present at additional synaptic locations, 91,171 suggesting roles in synaptic transmission.…”

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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“…MDS and the related isolated lissencephaly sequence (ILS) are diseases characterized by classical lissencephaly (smooth brain), a neuronal migration defect that results in mental retardation and epilepsy (Dobyns et al, 1993). MDS and ILS patients have hemizygous deletions in human chromosome 17p13.3, which results in the loss of sequences encoding LIS1 (Dobyns et al, 1993;Reiner et al, 1995), a protein involved in dynein motor function (Leventer et al, 2001). However, in MDS, the deletion is larger and is accompanied by a more severe lissencephaly with additional clinical symptoms, such as craniofacial defects (Chong et al, 1997;Dobyns et al, 1991).…”

Section: Spinocerebellar Ataxia Typementioning

confidence: 99%

Unlocking the code of 14-3-3

Dougherty¹,

Morrison²

2004

Journal of Cell Science

438

384

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One of the most striking `rags to riches' stories in the protein world is that of 14-3-3, originally identified in 1967 as merely an abundant brain protein. The first clues that 14-3-3 would play an important role in cell biology came almost 25 years later when it was found to interact with various proto-oncogene proteins and signaling proteins. The subsequent identification of 14-3-3 as a phosphoserine/phosphothreonine-binding protein firmly established its importance in cell signaling. 14-3-3 family members are found in all eukaryotes – from plants to mammals – and more than 100 binding partners have been identified to date. The targets of 14-3-3 are found in all subcellular compartments and their functional diversity is overwhelming – they include transcription factors, biosynthetic enzymes, cytoskeletal proteins, signaling molecules, apoptosis factors and tumor suppressors. 14-3-3 binding can alter the localization, stability, phosphorylation state, activity and/or molecular interactions of a target protein. Recent studies now indicate that the serine/threonine protein phosphatases PP1 and PP2A are important regulators of 14-3-3 binding interactions, and demonstrate a role for 14-3-3 in controlling the translocation of certain proteins from the cytoplasmic and endoplasmic reticulum to the plasma membrane. New reports also link 14-3-3 to several neoplastic and neurological disorders, where it might contribute to the pathogenesis and progression of these diseases.

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Lissencephaly gene (LIS1) expression in the CNS suggests a role in neuronal migration

Cited by 114 publications

References 30 publications

Impaired Learning and Motor Behavior in Heterozygous Pafah1b1 (Lis1) Mutant Mice

Impaired Learning and Motor Behavior in Heterozygous Pafah1b1 (Lis1) Mutant Mice

The DISC locus in psychiatric illness

Unlocking the code of 14-3-3

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