Article
Clinical Neurology
Christelle M. Durand, Chloe Angelini, Vincent Michaud, Claire Delleci, Isabelle Coupry, Cyril Goizet, Aurelien Trimouille
Summary: This study identified the genetic etiology of a patient with early onset sporadic progressive spastic ataxia and investigated the pathogenicity of VPS13D variants through functional studies. The findings confirmed the role of VPS13D in spastic ataxia and provided support for mitochondrial defects in patient's skin fibroblasts with VPS13D variants. The functional studies performed in this study could serve as biomarkers for diagnosis of VPS13D-related neurological disorders.
Review
Biochemistry & Molecular Biology
Jaya Bagaria, Eva Bagyinszky, Seong Soo A. An
Summary: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is an early-onset neurodegenerative disease that was originally discovered in Quebec. It is characterized by spasticity and ataxia, with retinal optic nerve hypermyelination being a common feature. Over 200 mutations in the SACS gene have been identified worldwide.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Nathalie Launay, Montserrat Ruiz, Laura Planas-Serra, Edgard Verdura, Agusti Rodriguez-Palmero, Agatha Schluter, Leire Goicoechea, Cristina Guilera, Josefina Casas, Felix Campelo, Emmanuelle Jouanguy, Jean-Laurent Casanova, Odile Boespflug-Tanguy, Maria Vazquez Cancela, Luis Gonzalez Gutierrez-Solana, Carlos Casasnovas, Estela Area-Gomez, Aurora Pujol
Summary: Rint1 is crucial for vesicular trafficking between the ER and Golgi apparatus. This study identified novel RINT1loss-of-function variants in 3 individuals with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features. Functional and lipidomic analyses revealed defective lipid-droplet biogenesis, lipid abnormalities, and mitochondrial dysfunction caused by RINT1 mutations.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Clinical Neurology
Yuliia V. Nikonishyna, Nadine J. Ortner, Teresa Kaserer, Jessica Hoffmann, Saskia Biskup, Manuel Dafotakis, Kathrin Reetz, Joerg B. Schulz, Jorg Striessnig, Maike F. Dohrn
Summary: The novel C256F variant in the Cav2.1 Ca2+ channel alpha 1-subunit is found to have pathogenicity in SCA, affecting channel function and contributing to the disease phenotype.
MOVEMENT DISORDERS
(2022)
Article
Medicine, General & Internal
Xin Huang, Dong-Sheng Fan
Summary: SCAR4 is a hereditary disease characterized by ataxia, pyramidal signs, neuropathy, and macrosaccadic intrusions. A novel compound heterozygous mutation, c.3288delA (p.Asp1097ThrfsTer6), in the VPS13D gene was reported in a young female Chinese patient, enriching the gene mutation spectrum associated with SCAR4.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Article
Clinical Neurology
Ahmed S. Emekli, Bedia Samanci, Gulsah Simsir, Hasmet A. Hanagasi, Hakan Gurvit, Basar Bilgic, A. Nazli Basak
Summary: Mutations in the PNPLA6 gene can lead to cerebellar ataxia and other syndromes, even in the absence of specific symptoms. Further studies are needed to understand the factors contributing to the phenotypic variability in patients with PNPLA6 gene mutations.
NEUROLOGICAL SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Samantha Katarzyna Dziurdzik, Elizabeth Conibear
Summary: The conserved VPS13 proteins are a new family of lipid transporters at membrane contact sites, with mutations in human homologs linked to neurological disorders. Yeast serves as a useful model system to study Vps13 function at different organelles and determine the factors responsible for its membrane targeting. Recent advances in understanding VPS13 proteins, focusing on yeast research, are described in this review.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Neurosciences
Mahmoud Reza Ashrafi, Pouria Mohammadi, Ali Reza Tavasoli, Morteza Heidari, Sareh Hosseinpour, Maryam Rasulinejad, Mohammad Rohani, Masoud Ghahvechi Akbari, Reza Azizi Malamiri, Reza Shervin Badv, Davood Fathi, Ali Zare Dehnavi, Shahram Savad, Ali Rabbani, Matthis Synofzik, Nejat Mahdieh, Zahra Rezaei
Summary: Autosomal recessive spastic ataxia of Charlevoix Saguenay (ARSACS) is one of the most common autosomal recessive ataxias, characterized by progressive cerebellar ataxia, spasticity, and sensorimotor polyneuropathy. However, not all patients exhibit the classic clinical triad. Brain magnetic resonance imaging (MRI) shows symmetric linear hypointensities in the pons and anterior superior cerebellar atrophy, as well as a hyperintense rim around the thalami. This study expands the molecular spectrum of ARSACS, identifying new genetic variants and reporting anterior temporal arachnoid cyst as a potential associated imaging feature.
Article
Biochemistry & Molecular Biology
Rui Alves, Maria Pazos-Gil, Marta Medina-Carbonero, Arabela Sanz-Alcazar, Fabien Delaspre, Jordi Tamarit
Summary: This study analyzed the conservation of structure and residues among frataxins and CyaY proteins, identifying four highly conserved residue clusters, with cluster 3 unique to eukaryotic frataxins and CyaY proteins from the Rickettsia genus. The tyrosine residue in cluster 3 is hypothesized to prevent the formation of reactive oxygen species during iron detoxification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Christopher M. Furman, Ting-Yi Wang, Qiuye Zhao, Kumar Yugandhar, Haiyuan Yu, Eric Alani
Summary: This study demonstrated that dynamic and coordinated rearrangements of the MLH IDRs regulate the function of the MLH complex positively and negatively in MMR.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Clinical Neurology
Yuzhi Shi, An Wang, Bin Chen, Xingao Wang, Songtao Niu, Wei Li, Shaowu Li, Zaiqiang Zhang
Summary: This study investigated the clinical features and genetic spectrum of patients with clinically suspected hereditary spastic paraplegia (HSP). It found that causative genetic mutations were identified in 51.9% of patients, with SPG4 and SPG11 being the most common gene mutations. Gait disturbance was the most common initial symptom, and there were overlapping clinical manifestations and neuroimaging findings between HSP and spinocerebellar ataxia (SCA).
FRONTIERS IN NEUROLOGY
(2022)
Article
Medicine, Research & Experimental
Tingting Li, Hongmin Cai, Yapei Zhao, Yanfang Li, Yanling Lai, Hebang Yao, Liu Daisy Liu, Zhou Sun, Martje Fentener van Vlissingen, Thijs Kuiken, Corine H. GeurtsvanKessel, Ning Zhang, Bingjie Zhou, Lu Lu, Yuhuan Gong, Wenming Qin, Moumita Mondal, Bowen Duan, Shiqi Xu, Audrey S. Richard, Herve Raoul, JianFeng Chen, Chenqi Xu, Ligang Wu, Haisheng Zhou, Zhong Huang, Xuechao Zhang, Jun Li, Yanyan Wang, Yuhai Bi, Barry Rockx, Junfang Chen, Fei-Long Meng, Dimitri Lavillette, Dianfan Li
Summary: The non-RBM-targeting monoclonal antibody FD20 isolated from convalescent patients neutralizes SARS-CoV-2, including Variants of Concern. It engages the RBD at a distal epitope, coinciding with a predicted vulnerability site. The antibody's mechanism of neutralization involves destructing the Spike protein, showing potential for antiviral drug development.
EMBO MOLECULAR MEDICINE
(2021)
Article
Clinical Neurology
Ikhlass Haj Salem, Marie Beaudin, Monica Stumpf, Mehrdad A. Estiar, Pierre-Olivier Cote, Francis Brunet, Pierre-Luc Gamache, Guy A. Rouleau, Karim Mourabit-Amari, Ziv Gan-Or, Nicolas Dupre
Summary: The study estimated the minimum prevalence of genetically defined adult hereditary ataxias and spastic paraplegias in Eastern Quebec. Around half of the patients had a confirmed genetic diagnosis, with AR cerebellar ataxia type 1 and AD spastic paraplegia SPG4 being the most prevalent disorders identified.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2021)
Article
Genetics & Heredity
Yangying Jia, Jianhai Chen, Jie Zhong, Xuefei He, Li Zeng, Yanmin Wang, Jiakun Li, Shengqian Xia, Erdengqieqieke Ye, Jing Zhao, Bin Ke, Chunyu Li
Summary: Hypoplastic left heart syndrome (HLHS) is a rare and fatal birth defect. A study identified a mutation in the PTPRB gene associated with HLHS.
Article
Chemistry, Multidisciplinary
Ammar Ammar, Rachel Cavill, Chris Evelo, Egon Willighagen
Summary: A large database of 0.6 million mutated binding site protein-ligand complexes, called PSnpBind, has been constructed to provide a reference dataset for studying the effects of natural variants on drug targets. This database is important for developing machine learning algorithms and studying protein-ligand affinity.
JOURNAL OF CHEMINFORMATICS
(2022)
Article
Cell Biology
Bjorn D. M. Bean, Samantha K. Dziurdzik, Kathleen L. Kolehmainen, Claire M. S. Fowler, Waldan K. Kwong, Leslie I. Grad, Michael Davey, Cayetana Schluter, Elizabeth Conibear
JOURNAL OF CELL BIOLOGY
(2018)
Article
Cell Biology
Sai T. Dharwada, Lauren E. Dalton, Bjorn D. M. Bean, Nirmala Padmanabhan, Catherine Choi, Cayetana Schluter, Michael Davey, Elizabeth Conibear
Meeting Abstract
Biochemistry & Molecular Biology
Idil Ulengin-Talkish, Rachel Bond, Nicole St-Denis, Anne-Claude Gingras, Alexis Shih, Elizabeth Conibear, Tamas Balla, Peter Varnai, Martha Cyert
Review
Biochemistry & Molecular Biology
Samantha Katarzyna Dziurdzik, Elizabeth Conibear
Summary: The conserved VPS13 proteins are a new family of lipid transporters at membrane contact sites, with mutations in human homologs linked to neurological disorders. Yeast serves as a useful model system to study Vps13 function at different organelles and determine the factors responsible for its membrane targeting. Recent advances in understanding VPS13 proteins, focusing on yeast research, are described in this review.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Idil Ulengin-Talkish, Matthew A. H. Parson, Meredith L. Jenkins, Jagoree Roy, Alexis Z. L. Shih, Nicole St-Denis, Gergo Gulyas, Tamas Balla, Anne-Claude Gingras, Peter Varnai, Elizabeth Conibear, John E. Burke, Martha S. Cyert
Summary: Calcineurin, a phosphatase regulated by calcium and targeted by immunosuppressants, is involved in regulating GPCR-mediated phospholipid signaling. A less-studied isoform of calcineurin, CNA beta 1, was found to localize to the plasma membrane through palmitoylation and promote the activity of PI4KA complex. This work reveals a calcineurin-regulated signaling pathway involving the PI4KA complex and highlights the importance of dynamic palmitoylation in conferring unique localization and regulation to CNA beta 1.
NATURE COMMUNICATIONS
(2021)
Article
Cell Biology
Shawn P. Shortill, Mia S. Frier, Elizabeth Conibear
Summary: The endolysosomal network is a dynamic membrane structure that controls cellular degradation and recycling. SNX-BAR proteins, a family of endosomal coat complexes, can directly recognize and deliver cargo without the need for association with retromer complex. This review also investigates their functional overlap with other complexes and factors.
CURRENT OPINION IN CELL BIOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Martha Cyert, Idil Ulengin-Talkish, Matthew A. Parson, Meredith L. Jenkins, Jagoree Roy, Alexis Z. Shih, Nicole St-Denis, Gergo Gulyas, Tamas Balla, Anne-Claude Gingras, Peter Varnai
Article
Biology
Shawn P. Shortill, Mia S. Frier, Ponthakorn Wongsangaroonsri, Michael Davey, Elizabeth Conibear
Summary: Membrane trafficking pathways play important roles in establishing and maintaining the endosomal network. The cooperation between retromer and VARP guides the endosomal recycling pathway. In yeast cells, Vrl1 forms a complex named VINE with Vin1, exhibiting features of a SNX-BAR coat protein. The VINE complex redistributes proteins in the endosome.
Article
Biology
Ines Gomes Castro, Shawn P. Shortill, Samantha Katarzyna Dziurdzik, Angela Cadou, Suriakarthiga Ganesan, Rosario Valenti, Yotam David, Michael Davey, Carsten Mattes, Ffion B. Thomas, Reut Ester Avraham, Hadar Meyer, Amir Fadel, Emma J. Fenech, Robert Ernst, Vanina Zaremberg, Tim P. Levine, Christopher Stefan, Elizabeth Conibear, Maya Schuldiner
Summary: This study systematically characterized the proteomes of contact sites in Saccharomyces cerevisiae using co-localization imaging, identifying over 100 new potential residents and effectors. Several newly identified residents were found to play a role in the regulation of ergosterol distribution.
Review
Biochemistry & Molecular Biology
David Tse Shen Lin, Nicholas G. Davis, Elizabeth Conibear
BIOCHEMICAL SOCIETY TRANSACTIONS
(2017)