Publications by authors named "Natsuki Sasaki"

17 Publications

  • Page 1 of 1

Positional cloning and comprehensive mutation analysis identified a novel KDM2B mutation in a Japanese family with minor malformations, intellectual disability, and schizophrenia.

J Hum Genet 2021 Jun 6;66(6):597-606. Epub 2021 Jan 6.

Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

The importance of epigenetic control in the development of the central nervous system has recently been attracting attention. Methylation patterns of lysine 4 and lysine 36 in histone H3 (H3K4 and H3K36) in the central nervous system are highly conserved among species. Numerous complications of body malformations and neuropsychiatric disorders are due to abnormal histone H3 methylation modifiers. In this study, we analyzed a Japanese family with a dominant inheritance of symptoms including Marfan syndrome-like minor physical anomalies (MPAs), intellectual disability, and schizophrenia (SCZ). We performed positional cloning for this family using a single nucleotide polymorphism (SNP) array and whole-exome sequencing, which revealed a missense coding strand mutation (rs1555289644, NM_032590.4: c.2173G>A, p.A725T) in exon 15 on the plant homeodomain of the KDM2B gene as a possible cause of the disease in the family. The exome sequencing revealed that within the coding region, only a point mutation in KDM2B was present in the region with the highest logarithm of odds score of 2.41 resulting from whole genome linkage analysis. Haplotype analysis revealed co-segregation with four affected family members (IV-9, III-4, IV-5, and IV-8). Lymphoblastoid cell lines from the proband with this mutation showed approximately halved KDM2B expression in comparison with healthy controls. KDM2B acts as an H3K4 and H3K36 histone demethylase. Our findings suggest that haploinsufficiency of KDM2B in the process of development, like other H3K4 and H3K36 methylation modifiers, may have caused MPAs, intellectual disability, and SCZ in this Japanese family.
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http://dx.doi.org/10.1038/s10038-020-00889-4DOI Listing
June 2021

Pyrexia by COVID-19 in a patient treated with dabrafenib/trametinib therapy.

J Dermatol 2021 Feb 16;48(2):e122-e123. Epub 2020 Nov 16.

Department of Dermatology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan.

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http://dx.doi.org/10.1111/1346-8138.15696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753748PMC
February 2021

Service Needs of Older Adults with Serious Mental Illness.

J Gerontol Soc Work 2020 Aug-Oct;63(6-7):659-661. Epub 2020 May 15.

Places for People, Inc ., Saint Louis, Missouri, USA.

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http://dx.doi.org/10.1080/01634372.2020.1765064DOI Listing
February 2021

Contents and Intensity of Services in Low- and High-Fidelity Programs for Supported Employment: Results of a Longitudinal Survey.

Psychiatr Serv 2020 05 3;71(5):472-479. Epub 2020 Jan 3.

Department of Community Mental Health & Law, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo (Yamaguchi, Sato, Matsunaga, Shimodaira, Fujii); Department of Education for Childcare, Faculty of Child Studies, Tokyo Kasei University, Tokyo (Mizuno); Brown School, Washington University in Saint Louis, St. Louis (Sasaki).

Objective: Little is known about the association between service intensity and fidelity scale score in supported employment programs. This study compares service contents and intensity in low- and high-fidelity programs and examines the validity of the Japanese version of the individualized Supported Employment Fidelity Scale.

Methods: The vocational outcomes and service provision data for 51 individuals with schizophrenia in 13 supported employment programs were collected over a 12-month study period. Outcomes, service contents, and service intensity were compared between the low-fidelity group (seven programs; N=29) and the high-fidelity group (six programs; N=22).

Results: In both groups, 70% of the total services (hours) were provided in the first 6 months. The high-fidelity group, which was associated with better vocational outcomes than the low-fidelity group (employment rate, 68% versus 38%, respectively), made the greatest effort in job development outside of the agency, whereas the low-fidelity group spent more time on group services. In addition, before the client obtained a job, high-fidelity programs provided outreach services (B=7.2, p=0.043) and agency-based individual services (B=5.7, p<0.001) at greater intensity than did low-fidelity programs. However, no significant between-group difference was found in service intensity once clients were employed.

Conclusions: Supported employment programs with a high fidelity score focus more intensely on providing individual services in and outside of the agency, particularly before clients obtain a job. However, clarification of the relationships among service quality at the structure level, amount of follow-up services, and individual needs in supported employment programs is a future issue.
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http://dx.doi.org/10.1176/appi.ps.201900255DOI Listing
May 2020

Novel pathogenic mutations in McLeod syndrome and interaction between XK protein and chorein.

Neurol Genet 2019 Jun 22;5(3):e328. Epub 2019 Apr 22.

Department of Psychiatry (Y. Urata, M.N., N. Sasaki, N. Shiokawa, Y. Nishida, K.A., H.H., I.Y., A.S.), Kagoshima University Graduate School of Medical and Dental Sciences; Department of Neurology and Gerontology (S.N., Y.T.), Iwate Medical University, Morioka; Department of Neurology (T.M.), School of Medicine, Fukushima Medical University; Department of Neuro-regeneration, Department of Neurology (Y. Ugawa), School of Medicine, Fukushima Medical University; Department of Neurology (H.S., S.K.), Kansai Medical University, Hirakata; Department of Neurology (Y. Nakazawa, R.Y., S.S.), Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka; Department of Neurology (T.S.), Nagano Matsushiro General Hospital; and Department of General Medicine (H.A.), Nagano Matsushiro General Hospital, Japan.

Objective: To identify pathologic mutations in 6 patients with suspected McLeod syndrome (MLS) and a possible interaction between the chorea-acanthocytosis (ChAc)- and MLS-responsible proteins: chorein and XK protein.

Methods: Erythrocyte membrane proteins from patients with suspected MLS and patients with ChAc, ChAc mutant carriers, and normal controls were analyzed by XK and chorein immunoblotting. We performed mutation analysis and XK immunoblotting to molecularly diagnose the patients with suspected MLS. Lysates of cultured cells were co-immunoprecipitated with anti-XK and anti-chorein antibodies.

Results: All suspected MLS cases were molecularly diagnosed with MLS, and novel mutations were identified. The average onset age was 46.8 ± 8 years, which was older than that of the patients with ChAc. The immunoblot analysis revealed remarkably reduced chorein immunoreactivity in all patients with MLS. The immunoprecipitation analysis indicated a direct or indirect chorein-XK interaction.

Conclusions: In this study, pathogenic mutations were identified in all 6 MLS cases, including novel mutations. Chorein immunoreactions were significantly reduced in MLS erythrocyte membranes. In addition, we demonstrated a possible interaction between the chorein and XK protein via molecular analysis. The reduction in chorein expression is similar to that between Kell antigens and XK protein, although the chorein-XK interaction is a possibly noncovalent binding unlike the covalent Kell-XK complex. Our results suggest that reduced chorein levels following lack of XK protein are possibly associated with molecular pathogenesis in MLS.
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http://dx.doi.org/10.1212/NXG.0000000000000328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6481271PMC
June 2019

Development of a scale to assess motivation for competitive employment among persons with severe mental illness.

PLoS One 2018 2;13(10):e0204809. Epub 2018 Oct 2.

Department of Mental Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.

Background: The employment rate among people with severe mental illness has recently increased, though it is still low. The motivation to work appears to be an important role as an intermediate outcome measure in vocational rehabilitation programs. In addition, measuring the work motivation for people with severe mental illness appears to be essential to identify candidates who are likely to benefit and monitor candidates' motivation in a supported employment program. This study aimed to develop a new measure for assessing both intrinsic and extrinsic motivation to work among people with severe mental illness, as there are currently no well-established instruments of this kind.

Methods: A focus group interview and review of previous qualitative research were used to identify possible items for inclusion in the new scale. A provisional scale was constructed and further refined for content and format based on feedback from a researcher and also three peer workers with severe mental illness. The resulting provisional 38-item version of the scale was completed by 136 respondents with severe mental illness, and we performed exploratory factor analysis to identify latent constructs within the new measure. The finalized scale was analyzed for test-retest reliability, internal consistency, and convergent validity.

Result: An exploratory factor analysis yielded a four-factor scale with 23 items. The finalized 23 items had high internal consistency (Cronbach's alpha = 0.91) and relatively high test-retest reliability (ICC = 0.83). The four subscales had fair internal consistency (Cronbach's alpha ≥ 0.69) and good test-retest reliability (ICC ≥ 0.61). Convergent validity was weakly supported by the significant positive correlations with the overall question on motivation to work (r ≥ 0.19, p < 0.01). Besides these correlations, only the "Pressure from others" subscale was negatively and significantly correlated with the negative symptoms evaluated using the Positive and Negative Syndrome Scale (r = -0.18, p = 0.04).

Conclusions: This study used factor analysis to develop a new multidimensional scale assessing motivation for competitive employment among persons with severe mental illness. The scale showed acceptable levels of reliability and factor-based and convergent validity. The new measure can be used for measuring the motivation for competitive employment among people with severe mental illness, and it would be useful to identify candidates who are likely to benefit from a certain supported employment program, and to monitor interim progress of the state of participants' motivation in a program.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0204809PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168136PMC
March 2019

Mouse model of chorea-acanthocytosis exhibits male infertility caused by impaired sperm motility as a result of ultrastructural morphological abnormalities in the mitochondrial sheath in the sperm midpiece.

Biochem Biophys Res Commun 2018 09 21;503(2):915-920. Epub 2018 Jun 21.

Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.

Chorea-acanthocytosis (ChAc) is an autosomal recessive hereditary disease characterized by neurodegeneration in the striatum and acanthocytosis caused by loss-of-function mutations in the Vacuolar Protein Sorting 13 Homolog A (VPS13A) gene, which encodes chorein. We previously produced a ChAc-model mouse with a homozygous deletion of exons 60-61 in Vps13a, which corresponded to the human disease mutation. We found that male ChAc-model mice exhibited complete infertility as a result of severely diminished sperm motility. Immunocytochemical study revealed that chorein-like immunoreactivity is abundant only in the midpiece, mitochondria-rich region, of the sperm of wild type mice. They showed no significant differences from wild types in terms of the adenosine 5'-triphosphate (ATP) concentration of their sperm, sperm count, or sexual activity. Electron microscopy revealed abnormal ultrastructural morphology of the mitochondria in the midpiece of sperm from ChAc-model mice. These results suggest that chorein is essential in mouse sperm for the maintenance of ultrastructural mitochondrial morphology and sperm motility.
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http://dx.doi.org/10.1016/j.bbrc.2018.06.096DOI Listing
September 2018

Development and Validation of a Japanese Fidelity Scale for Supported Employment.

Adm Policy Ment Health 2018 03;45(2):318-327

Department of Psychiatric Rehabilitation, National Institute of Mental Health, National Center of Neurology and Psychiatry (NCNP), 4-1-1 Ogawa-Higashi, Kodaira, Tokyo, 187-8553, Japan.

The Individual Placement and Support (IPS) model of supported employment is an evidence based practice. Although several agencies have been trying to implement the IPS-model since 2005 in Japan, there was no tool to assess the quality. This study developed a Japanese version of the 25-item Individualized Supported Employment Fidelity Scale (J-ISEF), a new Japanese fidelity tool for supported employment based on the IPS model. A working group consisting of researchers and practitioners was formed to develop J-ISEF based on IPS-25. Some experts of the group visited the community agencies in Vermont before the development process. Twenty-six eligible agencies were identified using snowball sampling, and 14 agencies of them agreed and participated at T1. We conducted three cross-sectional surveys (T1, T2 and T3), using the new scale. The first evaluation period (T1) was between September 2013 and February 2014, the second (T2) between September 2014 and February 2015, and the third (T3) between October 2015 and February 2016. High inter-rater reliability (ICC = 0.98 for the entire scale) was confirmed from T1 data. The total score and the service subscale total were positively correlated with employment rate (P < 0.05). A new fidelity scale, J-ISEF, is developed as a quality assessment tool for evidence-based supported employment programs in Japan. The evidence for its inter-rater reliability and criterion-related validity is promising.
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http://dx.doi.org/10.1007/s10488-017-0825-yDOI Listing
March 2018

Efficacy of a Peer-Led, Recovery-Oriented Shared Decision-Making System: A Pilot Randomized Controlled Trial.

Psychiatr Serv 2017 Dec 15;68(12):1307-1311. Epub 2017 Sep 15.

Dr. Yamaguchi, Dr. Taneda, Ms. Matsunaga, Ms. Sasaki, Dr. Mizuno, and Dr. Ito are with the Department of Psychiatric Rehabilitation, National Center of Neurology and Psychiatry, National Institute of Mental Health, Kodaira, Tokyo. Ms. Sawada is with the Graduate School of Social Welfare, Japan College of Social Work, Kiyose, Tokyo. Dr. Sakata is with the Department of Psychiatry, National Center of Neurology and Psychiatry Hospital, Kodaira, Tokyo. Dr. Fukui is with the Department of Educational Psychology, Tokyo Gakugei University, Koganei, Tokyo. Ms. Hisanaga is with the Community Mental Health and Welfare Bonding Organization, Ichikawa, Chiba, Japan. Mr. Bernick is with the Student Accessibility Office, Nagasaki University, Nagasaki, Nagasaki, Japan.

Objective: The effects of a comprehensive shared decision-making system based on the CommonGround approach and incorporating peer support and a computerized decision aid were investigated.

Methods: A pilot randomized controlled trial with six-month follow-up was conducted in Japan. Fifty-six outpatients with mental illness were randomly allocated to a shared decision-making system (intervention) group or treatment as usual (control) group. The implementation process and several outcomes were compared between groups.

Results: The core components and processes of shared decision making were observed in the intervention group more frequently than in the control group. The intervention group also reported a significantly more positive participants' view of the relationship with their doctor than the control group. The intervention did not have a significant effect on most clinical and recovery-related outcomes.

Conclusions: The shared decision-making system appeared to partly improve patients' perceptions of communication and relationships with doctors but did not have a significant effect on other patient-level outcomes.
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http://dx.doi.org/10.1176/appi.ps.201600544DOI Listing
December 2017

Identification of liver-specific enhancer-promoter activity in the 3' untranslated region of the wild-type AAV2 genome.

Nat Genet 2017 Aug 19;49(8):1267-1273. Epub 2017 Jun 19.

Gene Therapy Research Unit, Children's Medical Research Institute and Sydney Children's Hospitals Network, University of Sydney, Sydney, New South Wales, Australia.

Vectors based on adeno-associated virus type 2 (AAV2) are powerful tools for gene transfer and genome editing applications. The level of interest in this system has recently surged in response to reports of therapeutic efficacy in human clinical trials, most notably for those in patients with hemophilia B (ref. 3). Understandably, a recent report drawing an association between AAV2 integration events and human hepatocellular carcinoma (HCC) has generated controversy about the causal or incidental nature of this association and the implications for AAV vector safety. Here we describe and functionally characterize a previously unknown liver-specific enhancer-promoter element in the wild-type AAV2 genome that is found between the stop codon of the cap gene, which encodes proteins that form the capsid, and the right-hand inverted terminal repeat. This 124-nt sequence is within the 163-nt common insertion region of the AAV genome, which has been implicated in the dysregulation of known HCC driver genes and thus offers added insight into the possible link between AAV integration events and the multifactorial pathogenesis of HCC.
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http://dx.doi.org/10.1038/ng.3893DOI Listing
August 2017

Chorein interacts with α-tubulin and histone deacetylase 6, and overexpression preserves cell viability during nutrient deprivation in human embryonic kidney 293 cells.

FASEB J 2016 11 28;30(11):3726-3732. Epub 2016 Jul 28.

Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

The autophagy pathway has recently been implicated in several neurodegenerative diseases. Recently, it was reported that chorein-depleted cells showed accumulation of autophagic markers and impaired autophagic flux. Here, we demonstrate that chorein overexpression preserves cell viability from starvation-induced cell death in human embryonic kidney 293 (HEK293) cells. Subsequent coimmunoprecipitation and reverse coimmunoprecipitation assays using extracts from chorein that stably overexpressed HEK293 cells revealed that chorein interacts with α-tubulin and histone deacetylase 6, a known α-tubulin deacetylater and central component of basal autophagy. Indeed, acetylated α-tubulin immunoreactivity was significantly decreased in chorein that stably overexpressed HEK293 cells. These results suggest that chorein/histone deacetylase 6/α-tubulin interactions may play an important role in starvation-induced cell stress, and their disruption may be one of the molecular pathogenic mechanisms of chorea-acanthocytosis.-Sasaki, N., Nakamura, M., Kodama, A., Urata, Y., Shiokawa, N., Hayashi, T., Sano, A. Chorein interacts with α-tubulin and histone deacetylase 6, and overexpression preserves cell viability during nutrient deprivation in human embryonic kidney 293 cells.
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http://dx.doi.org/10.1096/fj.201500191RRDOI Listing
November 2016

The experience of electroconvulsive therapy and its impact on associated stigma: A meta-analysis.

Int J Soc Psychiatry 2016 Dec 26;62(8):708-718. Epub 2016 Oct 26.

Department of Neuropsychiatry, NTT Medical Center Tokyo, Tokyo, Japan

Background: Despite its efficacy and safety, electroconvulsive therapy (ECT) is underutilized, in part due to stigma associated with the treatment.

Aims: The aim of this study was to test the hypothesis that experiencing ECT has an impact on associated stigma, as measured by patient and family knowledge of and attitudes toward ECT.

Methods: A comprehensive literature search was conducted using MEDLINE, EMBASE and PsycINFO. Studies with cross-sectional and/or longitudinal designs were identified. Studies were further categorized into subcategories based on participant type (patients or patient family members) and outcome domain (knowledge or attitudes). Effect size (Cohen's d) was calculated for each study and then integrated into each subcategory (participant type by outcome domain) using a random effect model.

Results: Eight studies were identified as being eligible for analysis. Two studies were cross-sectional, five were longitudinal and one incorporated both designs. Analysis of the longitudinal studies indicated that experiencing ECT both increased knowledge of and improved attitudes toward ECT in patients; in family members of patients, analysis showed significant positive change in knowledge of ECT, but no significant change in attitudes toward ECT.

Conclusion: Experience with ECT may have a positive impact on knowledge of and attitudes toward ECT. However, the quality of evidence of included studies was low; further research is required in order to clarify the relationship and to identify information of use to individuals considering ECT as a treatment option.
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http://dx.doi.org/10.1177/0020764016675379DOI Listing
December 2016

Quantitative assays for measuring human telomerase activity and DNA binding properties.

Methods 2017 02 6;114:85-95. Epub 2016 Aug 6.

Children's Medical Research Institute, 214 Hawkesbury Rd, Westmead, NSW 2145, Australia; University of Sydney, Sydney, NSW 2006, Australia. Electronic address:

Telomerase is the ribonucleoprotein enzyme that catalyzes the processive addition of the telomeric DNA repeat 5'-TTAGGG-3' onto chromosome ends. In addition to its fascinating biochemical and enzymatic properties, clinical interest in telomerase stems from its dysregulated expression in ∼90% of human cancers, representing a broad spectrum of diseases. Exploiting telomerase as a therapeutic target and hence identifying and/or evaluating potential inhibitors requires quantitative measurement of its activity. This article presents procedures for measuring multiple aspects of telomerase enzymology that are relevant to both fundamental biochemistry and drug discovery: direct activity assays, DNA binding affinity, DNA dissociation, and cell-based over-expression of the active enzyme complex.
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http://dx.doi.org/10.1016/j.ymeth.2016.08.002DOI Listing
February 2017

Telomeric G-quadruplexes are a substrate and site of localization for human telomerase.

Nat Commun 2015 Jul 9;6:7643. Epub 2015 Jul 9.

Children's Medical Research Institute, University of Sydney, 214 Hawkesbury Road, Westmead, New South Wales 2145, Australia.

It has been hypothesized that G-quadruplexes can sequester the 3' end of the telomere and prevent it from being extended by telomerase. Here we purify and characterize stable, conformationally homogenous human telomeric G-quadruplexes, and demonstrate that human telomerase is able to extend parallel, intermolecular conformations in vitro. These G-quadruplexes align correctly with the RNA template of telomerase, demonstrating that at least partial G-quadruplex resolution is required. A highly purified preparation of human telomerase retains this extension ability, establishing that the core telomerase enzyme complex is sufficient for partial G-quadruplex resolution and extension. The parallel-specific G-quadruplex ligand N-methyl mesoporphyrin IX (NMM) causes an increase in telomeric G-quadruplexes, and we show that telomerase colocalizes with a subset of telomeric G-quadruplexes in vivo. The ability of telomerase to partially unwind, extend and localize to these structures implies that parallel telomeric G-quadruplexes may play an important biological role.
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http://dx.doi.org/10.1038/ncomms8643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4510649PMC
July 2015

Modeling correction of severe urea cycle defects in the growing murine liver using a hybrid recombinant adeno-associated virus/piggyBac transposase gene delivery system.

Hepatology 2015 Aug 23;62(2):417-28. Epub 2015 May 23.

Gene Therapy Research Unit, Children's Medical Research Institute and The Children's Hospital at Westmead, Westmead, New South Wales, Australia.

Unlabelled: Liver-targeted gene therapy based on recombinant adeno-associated viral vectors (rAAV) shows promising therapeutic efficacy in animal models and adult-focused clinical trials. This promise, however, is not directly translatable to the growing liver, where high rates of hepatocellular proliferation are accompanied by loss of episomal rAAV genomes and subsequently a loss in therapeutic efficacy. We have developed a hybrid rAAV/piggyBac transposon vector system combining the highly efficient liver-targeting properties of rAAV with stable piggyBac-mediated transposition of the transgene into the hepatocyte genome. Transposition efficiency was first tested using an enhanced green fluorescent protein expression cassette following delivery to newborn wild-type mice, with a 20-fold increase in stably gene-modified hepatocytes observed 4 weeks posttreatment compared to traditional rAAV gene delivery. We next modeled the therapeutic potential of the system in the context of severe urea cycle defects. A single treatment in the perinatal period was sufficient to confer robust and stable phenotype correction in the ornithine transcarbamylase-deficient Spf(ash) mouse and the neonatal lethal argininosuccinate synthetase knockout mouse. Finally, transposon integration patterns were analyzed, revealing 127,386 unique integration sites which conformed to previously published piggyBac data.

Conclusion: Using a hybrid rAAV/piggyBac transposon vector system, we achieved stable therapeutic protection in two urea cycle defect mouse models; a clinically conceivable early application of this technology in the management of severe urea cycle defects could be as a bridging therapy while awaiting liver transplantation; further improvement of the system will result from the development of highly human liver-tropic capsids, the use of alternative strategies to achieve transient transposase expression, and engineered refinements in the safety profile of piggyBac transposase-mediated integration.
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http://dx.doi.org/10.1002/hep.27842DOI Listing
August 2015

Chorein, the protein responsible for chorea-acanthocytosis, interacts with β-adducin and β-actin.

Biochem Biophys Res Commun 2013 Nov 12;441(1):96-101. Epub 2013 Oct 12.

Department of Psychiatry, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.

Chorea-acanthocytosis (ChAc) is an autosomal, recessive hereditary disease characterized by striatal neurodegeneration and acanthocytosis, and caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene. VPS13A encodes chorein whose physiological function at the molecular level is poorly understood. In this study, we show that chorein interacts with β-adducin and β-actin. We first compare protein expression in human erythrocyte membranes using proteomic analysis. Protein levels of β-adducin isoform 1 and β-actin are markedly decreased in erythrocyte membranes from a ChAc patient. Subsequent co-immunoprecipitation (co-IP) and reverse co-IP assays using extracts from chorein-overexpressing human embryonic kidney 293 (HEK293) cells, shows that β-adducin (isoforms 1 and 2) and β-actin interact with chorein. Immunocytochemical analysis using chorein-overexpressing HEK293 cells demonstrates co-localization of chorein with β-adducin and β-actin. In addition, immunoreactivity of β-adducin isoform 1 is significantly decreased in the striatum of gene-targeted ChAc-model mice. Adducin and actin are membrane cytoskeletal proteins, involved in synaptic function. Expression of β-adducin is restricted to the brain and hematopoietic tissues, corresponding to the main pathological lesions of ChAc, and thereby implicating β-adducin and β-actin in ChAc pathogenesis.
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http://dx.doi.org/10.1016/j.bbrc.2013.10.011DOI Listing
November 2013
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