当前位置： SCI文献检索 > HUMAN MOLECULAR GENETICS期刊下所有文献 > Parkinson's disease-linked DNAJC13 mutation aggravates alpha-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.

Parkinson's disease-linked DNAJC13 mutation aggravates alpha-synuclein-induced neurotoxicity through perturbation of endosomal trafficking.

Abstract：

:Mutations in DNAJC13 gene have been linked to familial form of Parkinson's disease (PD) with Lewy pathology. DNAJC13 is an endosome-related protein and believed to regulate endosomal membrane trafficking. However, the mechanistic link between DNAJC13 mutation and α-synuclein (αSYN) pathology toward neurodegeneration remains poorly understood. In this study, we showed that PD-linked N855S-mutant DNAJC13 caused αSYN accumulation in the endosomal compartment, presumably due to defective cargo trafficking from the early endosome to the late and/or recycling endosome. In vivo experiments using human αSYN transgenic flies showed that mutant DNAJC13 not only increased the amount of insoluble αSYN in fly head but also induced dopaminergic neurodegeneration, rough eye phenotype and age-dependent locomotor impairment. Together, these findings suggest that DNAJC13 mutation perturbs multi-directional endosomal trafficking, resulting in the aberrant endosomal retention of αSYN, which might predispose to the neurodegenerative process that leads to PD.

journal_name

Hum Mol Genet

journal_title

Human molecular genetics

authors

Yoshida S,Hasegawa T,Suzuki M,Sugeno N,Kobayashi J,Ueyama M,Fukuda M,Ido-Fujibayashi A,Sekiguchi K,Ezura M,Kikuchi A,Baba T,Takeda A,Mochizuki H,Nagai Y,Aoki M

doi

10.1093/hmg/ddy003

subject

Has Abstract

pub_date

2018-03-01 00:00:00

pages

823-836

issue

5

eissn

0964-6906

issn

1460-2083

pii

4788599

journal_volume

27

pub_type

杂志文章

相关文献

HUMAN MOLECULAR GENETICS文献大全
  • Loss of CHCHD2 and CHCHD10 activates OMA1 peptidase to disrupt mitochondrial cristae phenocopying patient mutations.

    abstract：:Dominant mutations in the mitochondrial paralogs coiled-helix-coiled-helix (CHCHD) domain 2 (C2) and CHCHD10 (C10) were recently identified as causing Parkinson's disease and amyotrophic lateral sclerosis/frontotemporal dementia/myopathy, respectively. The mechanism by which they disrupt mitochondrial cristae, however...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddaa077

    authors： Liu YT,Huang X,Nguyen D,Shammas MK,Wu BP,Dombi E,Springer DA,Poulton J,Sekine S,Narendra DP

    更新日期：2020-06-03 00:00:00

  • Altered palmitoylation and neuropathological deficits in mice lacking HIP14.

    abstract：:Huntingtin interacting protein 14 (HIP14, ZDHHC17) is a huntingtin (HTT) interacting protein with palmitoyl transferase activity. In order to interrogate the function of Hip14, we generated mice with disruption in their Hip14 gene. Hip14-/- mice displayed behavioral, biochemical and neuropathological defects that are ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr308

    authors： Singaraja RR,Huang K,Sanders SS,Milnerwood AJ,Hines R,Lerch JP,Franciosi S,Drisdel RC,Vaid K,Young FB,Doty C,Wan J,Bissada N,Henkelman RM,Green WN,Davis NG,Raymond LA,Hayden MR

    更新日期：2011-10-15 00:00:00

  • Allele-specific silencing of a pathogenic mutant acetylcholine receptor subunit by RNA interference.

    abstract：:Slow channel congenital myasthenic syndrome (SCCMS) is a disorder of the neuromuscular synapse caused by dominantly inherited missense mutations in genes that encode the muscle acetylcholine receptor (AChR) subunits. Here we investigate the potential of post-transcriptional gene silencing using RNA interference (RNAi)...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg280

    authors： Abdelgany A,Wood M,Beeson D

    更新日期：2003-10-15 00:00:00

  • Insight into Rett syndrome: MeCP2 levels display tissue- and cell-specific differences and correlate with neuronal maturation.

    abstract：:Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Previous data have shown that MECP2 RNA is present in all mouse and human tissues tested, but the timing of expression and regional distribution have not been explored. We investigated the spatial...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/11.2.115

    authors： Shahbazian MD,Antalffy B,Armstrong DL,Zoghbi HY

    更新日期：2002-01-15 00:00:00

  • The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1.

    abstract：:Mutations in the DFNB31 gene encoding the PDZ scaffold protein whirlin are causative for hearing loss in man and mouse. Whirlin is known to be essential for the elongation process of the stereocilia of sensory hair cells in the inner ear, though its complete spatial and temporal expression patterns remained elusive. H...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi490

    authors： van Wijk E,van der Zwaag B,Peters T,Zimmermann U,Te Brinke H,Kersten FF,Märker T,Aller E,Hoefsloot LH,Cremers CW,Cremers FP,Wolfrum U,Knipper M,Roepman R,Kremer H

    更新日期：2006-03-01 00:00:00

  • Functional characterization of SIM1-associated enhancers.

    abstract：:Haploinsufficiency of the single-minded homology 1 (SIM1) gene in humans and mice leads to severe obesity, suggesting that altered expression of SIM1, by way of regulatory elements such as enhancers, could predispose individuals to obesity. Here, we identified transcriptional enhancers that could regulate SIM1, using ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddt559

    authors： Kim MJ,Oksenberg N,Hoffmann TJ,Vaisse C,Ahituv N

    更新日期：2014-04-01 00:00:00

  • Drug repositioning as a therapeutic strategy for neurodegenerations associated with OPA1 mutations.

    abstract：:OPA1 mutations are the major cause of dominant optic atrophy (DOA) and the syndromic form DOA plus, pathologies for which there is no established cure. We used a 'drug repurposing' approach to identify FDA-approved molecules able to rescue the mitochondrial dysfunctions induced by OPA1 mutations. We screened two diffe...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddaa244

    authors： Aleo SJ,Del Dotto V,Fogazza M,Maresca A,Lodi T,Goffrini P,Ghelli A,Rugolo M,Carelli V,Baruffini E,Zanna C

    更新日期：2021-01-21 00:00:00

  • Homozygous mutation in the eukaryotic translation initiation factor 2alpha phosphatase gene, PPP1R15B, is associated with severe microcephaly, short stature and intellectual disability.

    abstract：:Protein translation is an essential cellular process initiated by the association of a methionyl-tRNA with the translation initiation factor eIF2. The Met-tRNA/eIF2 complex then associates with the small ribosomal subunit, other translation factors and mRNA, which together comprise the translational initiation complex...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddv337

    authors： Kernohan KD,Tétreault M,Liwak-Muir U,Geraghty MT,Qin W,Venkateswaran S,Davila J,Care4Rare Canada Consortium.,Holcik M,Majewski J,Richer J,Boycott KM

    更新日期：2015-11-15 00:00:00

  • Oncogenic conversion of a novel orphan nuclear receptor by chromosome translocation.

    abstract：:A recurrent t(9;22) (q22;q12) chromosome translocation has been described in extraskeletal myxoid chondrosarcoma (EMC). Fluorescent in situ hybridization experiments performed on one EMC tumour indicated that the chromosome 22 breakpoint occurred in the EWS gene. Northern blot analysis revealed an aberrant EWS transcr...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/4.12.2219

    authors： Labelle Y,Zucman J,Stenman G,Kindblom LG,Knight J,Turc-Carel C,Dockhorn-Dworniczak B,Mandahl N,Desmaze C,Peter M

    更新日期：1995-12-01 00:00:00

  • A common polymorphism decreases low-density lipoprotein receptor exon 12 splicing efficiency and associates with increased cholesterol.

    abstract：:Single nucleotide polymorphisms (SNPs) that alter exon splicing efficiency are an emerging class of functional genetic variants. Since mutations in low-density lipoprotein receptor (LDLR) are a primary cause of familial hypercholesterolemia, we evaluated whether LDLR SNPs may alter splicing efficiency and cholesterol ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm124

    authors： Zhu H,Tucker HM,Grear KE,Simpson JF,Manning AK,Cupples LA,Estus S

    更新日期：2007-07-15 00:00:00

  • C9orf72 poly GA RAN-translated protein plays a key role in amyotrophic lateral sclerosis via aggregation and toxicity.

    abstract：:An intronic GGGGCC (G4C2) hexanucleotide repeat expansion inC9orf72 is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of G4C2 RNA can result in five different dipeptide repeat proteins (DPR: poly GA, poly GP, poly GR, ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx350

    authors： Lee YB,Baskaran P,Gomez-Deza J,Chen HJ,Nishimura AL,Smith BN,Troakes C,Adachi Y,Stepto A,Petrucelli L,Gallo JM,Hirth F,Rogelj B,Guthrie S,Shaw CE

    更新日期：2017-12-15 00:00:00

  • PTEN inhibits insulin-stimulated MEK/MAPK activation and cell growth by blocking IRS-1 phosphorylation and IRS-1/Grb-2/Sos complex formation in a breast cancer model.

    abstract：:The tumour suppressor gene PTEN encodes a dual-specificity phosphatase that recognizes protein substrates and phosphatidylinositol-3,4,5-triphosphate. PTEN seems to play multiple roles in tumour suppression and the blockade of phosphoinositide-3-kinase signalling is important for its growth suppressive effects, althou...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/10.6.605

    authors： Weng LP,Smith WM,Brown JL,Eng C

    更新日期：2001-03-15 00:00:00

  • Evolution of the sperm methylome of primates is associated with retrotransposon insertions and genome instability.

    abstract：:Changes in gene expression resulting from epigenetic and/or genetic changes play an important role in the evolutionary divergence of phenotypes. To explore how epigenetic and genetic changes are linked during primate evolution, we have compared the genome-wide DNA methylation profiles (methylomes) of humans and chimpa...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddx236

    authors： Fukuda K,Inoguchi Y,Ichiyanagi K,Ichiyanagi T,Go Y,Nagano M,Yanagawa Y,Takaesu N,Ohkawa Y,Imai H,Sasaki H

    更新日期：2017-09-15 00:00:00

  • Naturally occurring germline and tumor-associated mutations within the ATP-binding motifs of PTEN lead to oxidative damage of DNA associated with decreased nuclear p53.

    abstract：:Somatic and germline mutations in PTEN (phosphatase and tensin homolog deleted on chromosome 10) are found in sporadic cancers and Cowden syndrome patients, respectively. Recent identification of naturally occurring cancer and germline mutations within the ATP-binding motifs of PTEN (heretofore referred to as PTEN ATP...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddq434

    authors： He X,Ni Y,Wang Y,Romigh T,Eng C

    更新日期：2011-01-01 00:00:00

  • Cerebral small-vessel disease protein HTRA1 controls the amount of TGF-β1 via cleavage of proTGF-β1.

    abstract：:Cerebral small-vessel disease is a common disorder in elderly populations; however, its molecular basis is not well understood. We recently demonstrated that mutations in the high-temperature requirement A (HTRA) serine peptidase 1 (HTRA1) gene cause a hereditary cerebral small-vessel disease, cerebral autosomal reces...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddr063

    authors： Shiga A,Nozaki H,Yokoseki A,Nihonmatsu M,Kawata H,Kato T,Koyama A,Arima K,Ikeda M,Katada S,Toyoshima Y,Takahashi H,Tanaka A,Nakano I,Ikeuchi T,Nishizawa M,Onodera O

    更新日期：2011-05-01 00:00:00

  • Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer's disease neurons: implications for mitochondrial dysfunction and neuronal damage.

    abstract：:We recently reported increased mitochondrial fission and decreased fusion, increased amyloid beta (Aβ) interaction with the mitochondrial fission protein Drp1, increased mitochondrial fragmentation, impaired axonal transport of mitochondria and synaptic degeneration in neurons affected by AD. In the present study, we ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds072

    authors： Manczak M,Reddy PH

    更新日期：2012-06-01 00:00:00

  • Changes in heparan sulfate are associated with delayed wound repair, altered cell migration, adhesion and contractility in the galactosyltransferase I (beta4GalT-7) deficient form of Ehlers-Danlos syndrome.

    abstract：:Reduced activity of beta4-galactosyltransferase 7 (beta4GalT-7), an enzyme involved in synthesizing the glycosaminoglycan linkage region of proteoglycans, is associated with the progeroid form of Ehlers-Danlos syndrome (EDS). In the invertebrates Drosophila melanogaster and Caenorhabditis elegans, mutations in beta4Ga...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddm372

    authors： Götte M,Spillmann D,Yip GW,Versteeg E,Echtermeyer FG,van Kuppevelt TH,Kiesel L

    更新日期：2008-04-01 00:00:00

  • Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes.

    abstract：:Mucopolysaccharidosis IVA (MPS IVA; OMIM#253000), a lysosomal storage disorder caused by a deficiency of N -acetylgalactosamine-6-sulfate sulfatase (GALNS), has variable clinical phenotypes. To date we have identified 65 missense mutations in the GALNS gene from MPS IVA patients, but the correlation between genotype a...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/9.9.1283

    authors： Sukegawa K,Nakamura H,Kato Z,Tomatsu S,Montaño AM,Fukao T,Toietta G,Tortora P,Orii T,Kondo N

    更新日期：2000-05-22 00:00:00

  • Direct measurement of the male recombination fraction in the human beta-globin hot spot.

    abstract：:Recombination was measured across nine intervals in the human beta-globin gene cluster by single-sperm analysis. A recombination fraction of approximately 0.9% was calculated across an approximately 11 kb region using a new method to estimate recombination fractions from single-sperm typing data. No recombination was ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/11.3.207

    authors： Schneider JA,Peto TE,Boone RA,Boyce AJ,Clegg JB

    更新日期：2002-02-01 00:00:00

  • The HLA class III subregion is responsible for an increased breast cancer risk.

    abstract：:BRCA1 and BRCA2 germline mutations account for <5% of breast cancer cases. Less penetrant breast cancer susceptibility genes are likely to exist. Earlier studies have suggested involvement of the HLA region. The HLA region was genotyped with 24 microsatellite markers and markers for two single nucleotide polymorphisms...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg245

    authors： de Jong MM,Nolte IM,de Vries EG,Schaapveld M,Kleibeuker JH,Oosterom E,Oosterwijk JC,van der Hout AH,van der Steege G,Bruinenberg M,Boezen HM,Te Meerman GJ,van der Graaf WT

    更新日期：2003-09-15 00:00:00

  • Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D).

    abstract：:Clinical, electrophysiological and genetic linkage studies were performed on a large autosomal dominant family with Charcot-Marie-Tooth axonal neuropathy type 2 (CMT2) with 38 members of which 14 were affected. Onset of the disease was between 16 and 30 years of age with weakness and atrophy of the hands more severe t...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/5.9.1373

    authors： Ionasescu V,Searby C,Sheffield VC,Roklina T,Nishimura D,Ionasescu R

    更新日期：1996-09-01 00:00:00

  • SPEG binds with desmin and its deficiency causes defects in triad and focal adhesion proteins.

    abstract：:SPEG, a member of the myosin light chain kinase family, is localized at the level of triad surrounding myofibrils in skeletal muscles. In humans, SPEG mutations are associated with centronuclear myopathy and cardiomyopathy. Using a striated muscle specific Speg-knockout (KO) mouse model, we have previously shown that ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddaa276

    authors： Luo S,Li Q,Lin J,Murphy Q,Marty I,Zhang Y,Kazerounian S,Agrawal PB

    更新日期：2020-12-23 00:00:00

  • Retinal development in Drosophila: specifying the first neuron.

    abstract：:In vertebrates, a proneural basic helix-loop-helix transcription factor (Ath5, Atonal homolog 5) plays a crucial role in the specification of the first retinal neuron: the retinal ganglion cell (RGC). Math5 homozygous null mutant mice lack RGCs and have no optic nerve. Furthermore, the expression of the Ath5 protein i...

    journal_title：Human molecular genetics

    pub_type： 杂志文章,评审

    doi：10.1093/hmg/11.10.1207

    authors： Hsiung F,Moses K

    更新日期：2002-05-15 00:00:00

  • Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3.

    abstract：:We have defined unexpectedly extensive copy number variation at the human anti-microbial alpha-defensin genes DEFA1 and DEFA3, encoding human neutrophil peptides HNP-1, HNP-2 and HNP-3. There was variation in both number and position of DEFA1/DEFA3 genes in arrays of 19 kb tandem repeats on 8p23.1, so that the DEFA1 a...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddi209

    authors： Aldred PM,Hollox EJ,Armour JA

    更新日期：2005-07-15 00:00:00

  • Involvement of the ubiquitin-proteasome pathway and molecular chaperones in oculopharyngeal muscular dystrophy.

    abstract：:Oculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant muscular dystrophy that results from small expansions of a polyalanine tract in the PABPN1 gene. Intranuclear inclusions are the pathological hallmark of OPMD. The mechanism by which protein aggregation in OPMD might relate to a toxic gain-of...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg293

    authors： Abu-Baker A,Messaed C,Laganiere J,Gaspar C,Brais B,Rouleau GA

    更新日期：2003-10-15 00:00:00

  • Alteration of performance in a mouse model of Emery-Dreifuss muscular dystrophy caused by A-type lamins gene mutation.

    abstract：:Autosomal Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in the lamin A/C gene (LMNA) encoding A-type nuclear lamins, intermediate filament proteins of the nuclear envelope. Classically, the disease manifests as scapulo-humero-peroneal muscle wasting and weakness, early joint contractures and dilated ...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddz056

    authors： Thomasson R,Vignier N,Peccate C,Mougenot N,Noirez P,Muchir A

    更新日期：2019-07-01 00:00:00

  • Loss of thymidine kinase 2 alters neuronal bioenergetics and leads to neurodegeneration.

    abstract：:Mutations of thymidine kinase 2 (TK2), an essential component of the mitochondrial nucleotide salvage pathway, can give rise to mitochondrial DNA (mtDNA) depletion syndromes (MDS). These clinically heterogeneous disorders are characterized by severe reduction in mtDNA copy number in affected tissues and are associated...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddq043

    authors： Bartesaghi S,Betts-Henderson J,Cain K,Dinsdale D,Zhou X,Karlsson A,Salomoni P,Nicotera P

    更新日期：2010-05-01 00:00:00

  • Direct interaction of the Fanconi anaemia protein FANCG with BRCA2/FANCD1.

    abstract：:Fanconi anaemia (FA) is an autosomal recessive genetic disorder characterized by progressive bone marrow failure, multiple congenital abnormalities, and an increased risk of cancer. FA cells are characterized by chromosomal instability and hypersensitivity to DNA interstrand crosslinking agents. At least eight complem...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddg266

    authors： Hussain S,Witt E,Huber PA,Medhurst AL,Ashworth A,Mathew CG

    更新日期：2003-10-01 00:00:00

  • A coding variant in CR1 interacts with APOE-ε4 to influence cognitive decline.

    abstract：:Complement receptor 1 (CR1) is an Alzheimer's disease (AD) susceptibility locus that also influences AD-related traits such as episodic memory decline and neuritic amyloid plaque deposition. We implemented a functional fine-mapping approach, leveraging intermediate phenotypes to identify functional variant(s) within t...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/dds054

    authors： Keenan BT,Shulman JM,Chibnik LB,Raj T,Tran D,Sabuncu MR,Alzheimer's Disease Neuroimaging Initiative.,Allen AN,Corneveaux JJ,Hardy JA,Huentelman MJ,Lemere CA,Myers AJ,Nicholson-Weller A,Reiman EM,Evans DA,Bennett DA,De J

    更新日期：2012-05-15 00:00:00

  • The unique transcriptome through day 3 of human preimplantation development.

    abstract：:Successful human development is dependent upon a cascade of events following fertilization. Unfortunately, knowledge of these critical events in humans is remarkably incomplete. Although hundreds of thousands of human embryos are cultured yearly at infertility centers worldwide, the vast majority fail to develop in cu...

    journal_title：Human molecular genetics

    pub_type： 杂志文章

    doi：10.1093/hmg/ddh157

    authors： Dobson AT,Raja R,Abeyta MJ,Taylor T,Shen S,Haqq C,Pera RA

    更新日期：2004-07-15 00:00:00