Molecular cloning of one isotype of human lamina-associated polypeptide 1s and a topological analysis using its deletion mutants

Kondo, Yukihiro; Kondoh, Junpei; Hayashi, Daisuke; Ban, Tadanobu; Takagi, Motoki; Kamei, Yasuhiro; Tsuji, Lyuji; Kim, Jiyoong; Yoneda, Yoshihiro

doi:10.1016/s0006-291x(02)00563-6

Cited by 41 publications

(40 citation statements)

References 46 publications

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“…They are homologous to each other in their C-terminal lumenal domains and bind via these to torsinA (15). There are three splice variants of LAP1 (LAP1A, LAP1B, and LAP1C) with differing N-terminal initia- tion sites that generate proteins with increasingly long N-terminal domains connected to a common transmembrane and lumenal domain (28,29). LAP1 isoforms are abundant proteins that bind to A-and B-type lamins (30, 31) but how they contribute to NE organization and/or function is still unknown.…”

Section: Resultsmentioning

confidence: 99%

Interaction of TorsinA with Its Major Binding Partners Is Impaired by the Dystonia-associated ΔGAG Deletion

Naismith

Dalal

Hanson

2009

Journal of Biological Chemistry

107

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Section: Resultsmentioning

confidence: 99%

Interaction of TorsinA with Its Major Binding Partners Is Impaired by the Dystonia-associated ΔGAG Deletion

Naismith

Dalal

Hanson

2009

Journal of Biological Chemistry

107

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“…LAP1B encoded by TOR1AIP1 is type-2 integral membrane protein located in the inner nuclear membrane binding both A-and B-type lamins and involved in the regulation of torsinA ATPase, a member of AAA + ATPase family (ATPases associated with a variety of cellular activities) known to be responsible for the severe movement disorder DYT1 dystonia [7][8][9][10][11][12]. TorsinA is diffusely distributed throughout the endoplasmic reticulum and the nuclear envelope continuity but some cell types exhibit a preference for the nuclear envelope [24,25].…”

Section: Discussionmentioning

confidence: 99%

“…To date, TOR1AIP1 (torsinA-interacting protein 1 gene) encoding LAP1B protein is the only cloned human lamina-associated polypeptide 1 [8]. Despite the fact that the function of LAP1B is currently not fully known, this type-2 integral membrane protein located in the inner nuclear membrane is known to bind both A-and B-type lamins [7][8][9][10]. Subsequently, LAP1 has been implicated in the regulation of torsinA ATPase which is known to cause the severe movement disorder DYT1 dystonia (MIM 128100) [11,12].…”

Section: Introductionmentioning

confidence: 99%

Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies

Kayman-Kurekci

Talim

Korkusuz

et al. 2014

Neuromuscular Disorders

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We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, rigid spine and contractures of the proximal and distal interphalangeal hand joints. Additionally, cardiomyopathy and respiratory involvement were noted. DNA sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina-associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We observed that expression of LAP1B was absent in the patient skeletal muscle fibres. Ultrastructural examination showed intact sarcomeric organization but alterations of the nuclear envelope including nuclear fragmentation, chromatin bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein localized in the inner nuclear membrane that binds to both A-and B-type lamins, and is involved in the regulation of torsinA ATPase. Interestingly, luminal domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA-was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the findings suggest that LAP1 and LULL1 might have a compensatory effect on each other. This study expands the spectrum of genes associated with nuclear envelopathies and highlights the critical function for LAP1B in striated muscle.

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“…A recent report utilizing torsinA mutant mice showed that LAP1 and torsinA act in the same biological pathway required for normal nuclear membrane morphology in both neuronal and non-neuronal cells (44). The C-terminal lumenal domain of LAP1B is highly conserved, but its function is unknown; the N-terminal nucleoplasmic domain and the transmembrane span of LAP1B are necessary and sufficient for the nuclear localization of the molecule (45). If the N-terminal nucleoplasmic domain is responsible for the interaction of LAP1s with lamins and chromosomes, the C-terminal lumenal domain is likely to play a regulatory role for the maintenance of the nuclear architecture and organization, which is likely to be modified by the AAAϩ activity of torsinA.…”

Section: Discussionmentioning

confidence: 99%

A Unique Redox-sensing Sensor II Motif in TorsinA Plays a Critical Role in Nucleotide and Partner Binding

Zhu

Millen

Mendoza

et al. 2010

Journal of Biological Chemistry

113

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Early onset dystonia is commonly associated with the deletion of one of a pair of glutamate residues (⌬E302/303) near the C terminus of torsinA, a member of the AAA؉ protein family (ATPases associated with a variety of cellular activities) located in the endoplasmic reticulum lumen. The functional consequences of the disease-causing mutation, ⌬E, are not currently understood. By contrast to other AAA؉ proteins, torsin proteins contain two conserved cysteine residues in the C-terminal domain, one of which is located in the nucleotide sensor II motif. Depending on redox status, an ATP hydrolysis mutant of torsinA interacts with lamina-associated polypeptide 1 (LAP1) and lumenal domain like LAP1 (LULL1). Substitution of the cysteine in sensor II diminishes the redox-regulated interaction of torsinA with these substrates. Significantly, the dystonia-causing mutation, ⌬E, alters the ability of torsinA to mediate the redox-regulated interactions with LAP1 and LULL1. Limited proteolysis experiments reveal redox-and mutation-dependent changes in the local conformation of torsinA as a function of nucleotide binding. These results indicate that the cysteinecontaining sensor II plays a critical role in redox sensing and the nucleotide and partner binding functions of torsinA and suggest that loss of this function of torsinA contributes to the development of DYT1 dystonia.Torsion dystonia is an autosomal dominant movement disorder that causes the muscles to contract and spasm involuntarily. These muscle contractions force the body into repetitive movements and often twisted postures. The most common and severe early onset form of dystonia has been linked to the mutations in the human DYT1 (TOR1A) gene encoding the protein torsinA (1, 2). Although the function of torsinA and the mechanism underlying dystonia disease remain obscure, the sequence of torsinA is homologous to a large and diverse group of ATP-dependent oligomeric proteins named the AAAϩ protein family. The AAAϩ proteins typically form oligomeric rings that catalyze a variety of cellular processes, including protein translocation, membrane trafficking, and conformational remodeling of regulatory factors (3-5). TorsinA is the founding member of a subfamily of AAAϩ proteins that includes torsinB (TOR1B) and two other related gene products (TOR2A and TOR3A) in mammals and OOC-5 in Caenorhabditis elegans (1, 6, 7).The signal sequence and the following hydrophobic region at the N terminus (Fig. 1A) target torsinA to the lumen of the endoplasmic reticulum (ER). 3 In the ER, torsinA perhaps acts on secreted (8, 9) or stress-related protein substrates (10). Unlike ClpA and ClpB, torsinA lacks a substrate-binding domain or other functional region outside its ATPase domain (11). Experimental evidence suggests that torsinA mediates varied cellular activities, including protection from toxic cellular stress (12-15), trafficking of membrane-associated proteins (16), and synaptic vesicle recycling (17). In this regard, torsinA regulates trafficking of a G-protein-coupled recept...

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Molecular cloning of one isotype of human lamina-associated polypeptide 1s and a topological analysis using its deletion mutants

Cited by 41 publications

References 46 publications

Interaction of TorsinA with Its Major Binding Partners Is Impaired by the Dystonia-associated ΔGAG Deletion

Interaction of TorsinA with Its Major Binding Partners Is Impaired by the Dystonia-associated ΔGAG Deletion

Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies

A Unique Redox-sensing Sensor II Motif in TorsinA Plays a Critical Role in Nucleotide and Partner Binding

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