ArticleProceedings of the National Academy of Sciences of the United States of America2018
MTSS1/Src family kinase dysregulation underlies multiple inherited ataxias.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Cerebellar Purkinje cell firing reduction contributes to aging-related declining motor coordination in mice.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Bibliometric analysis and core target identification of network pharmacology on neuroinflammation in central nervous system disorders: Trends, collaborations, and future directions.Neuroprotection (Chichester, England) · 2025Review
- PKCγ-mediated Phosphorylation of Mtss1 Regulates the Dendritic Outgrowth and Spine Development of Cerebellar Purkinje Cells.Molecular neurobiology · 2025Article
- Impairment of Hyaluronan-Related Glycocalyx Inhibits Macropinocytosis in Cancer Cells via p21 Upregulation.Biomacromolecules · 2025Article
- Establishment of a humanized SCA2 mouse model carrying a CAA disruption preventing CAG repeat expansion in pathogenic genes.Animal models and experimental medicine · 2025Article
- Spinocerebellar Ataxia Type 2: A Review and Personal Perspective.Neurology. Genetics · 2025Review
- The polyglutamine protein ATXN2: from its molecular functions to its involvement in disease.Cell death & disease · 2024Review
- AAV-Mediated CAG-Targeting Selectively Reduces Polyglutamine-Expanded Protein and Attenuates Disease Phenotypes in a Spinocerebellar Ataxia Mouse Model.International journal of molecular sciences · 2024Article
- Article
- Viewpoint: spinocerebellar ataxias as diseases of Purkinje cell dysfunction rather than Purkinje cell loss.Frontiers in molecular neuroscience · 2023Review
- Integrative Organelle-Based Functional Proteomics: In Silico Prediction of Impaired Functional Annotations inBiomolecules · 2022Article
- Metastasis suppressor 1 controls osteoblast differentiation and bone homeostasis through regulating Src-Wnt/β-catenin signaling.Cellular and molecular life sciences : CMLS · 2022Article
- Genetic landscape and autoimmunity of monocytes in developing Vogt-Koyanagi-Harada disease.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- miRNA-182 regulated MTSS1 inhibits proliferation and invasion in Glioma Cells.Journal of Cancer · 2020Article
- Receptor protein tyrosine phosphatases control Purkinje neuron firing.Cell cycle (Georgetown, Tex.) · 2020Article
- Differential interactions of missing in metastasis and insulin receptor tyrosine kinase substrate with RAB proteins in the endocytosis of CXCR4.The Journal of biological chemistry · 2019Article
- MIM-Deficient Mice Exhibit Anatomical Changes in Dendritic Spines, Cortex Volume and Brain Ventricles, and Functional Changes in Motor Coordination and Learning.Frontiers in molecular neuroscience · 2019Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
The genetically heterogeneous spinocerebellar ataxias (SCAs) are caused by Purkinje neuron dysfunction and degeneration, but their underlying pathological mechanisms remain elusive. The Src family of nonreceptor tyrosine kinases (SFK) are essential for nervous system homeostasis and are increasingly implicated in degenerative disease. Here we reveal that the SFK suppressor Missing-in-metastasis (MTSS1) is an ataxia locus that links multiple SCAs. MTSS1 loss results in increased SFK activity, reduced Purkinje neuron arborization, and low basal firing rates, followed by cell death. Surprisingly, mouse models for SCA1, SCA2, and SCA5 show elevated SFK activity, with SCA1 and SCA2 displaying dramatically reduced MTSS1 protein levels through reduced gene expression and protein translation, respectively. Treatment of each SCA model with a clinically approved Src inhibitor corrects Purkinje neuron basal firing and delays ataxia progression in MTSS1 mutants. Our results identify a common SCA therapeutic target and demonstrate a key role for MTSS1/SFK in Purkinje neuron survival and ataxia progression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.