ArticleFrontiers in neuroscience2019
Spastin MIT Domain Disease-Associated Mutations Disrupt Lysosomal Function.
Article in Frontiers in neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Reticulon-1 synthesis controls outgrowth and microtubule dynamics in injured cortical axons.Life science alliance · 2026Article
- 4-Phenylbutyric Acid Improves Gait Ability of UBAP1-Related Spastic Paraplegia Mouse Model: Therapeutic Potential for SPG80.International journal of molecular sciences · 2025Article
- Allosteric regulation of proteolytic machines unveiled by the synergy between cryo-EM and solution NMR spectroscopy.The Biochemical journal · 2025Review
- Targeting MDM2 affects spastin protein levels and functions: implications for HSP treatment.Cell death discovery · 2025Article
- IST1 regulates select recycling pathways.Traffic (Copenhagen, Denmark) · 2024Article
- Microtubule stabilising peptides: new paradigm towards management of neuronal disorders.RSC medicinal chemistry · 2023Review
- Genome-wide prediction of disease variant effects with a deep protein language model.Nature genetics · 2023Article
- Identification of a Novel Idiopathic Epilepsy Risk Locus and a Variant in theAnimals : an open access journal from MDPI · 2023Article
- Transverse endoplasmic reticulum expansion in hereditary spastic paraplegia corticospinal axons.Human molecular genetics · 2022Article
- Friction-driven membrane scission by the human ESCRT-III proteins CHMP1B and IST1.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- New spinocerebellar ataxia subtype caused byBrain communications · 2022Article
- Molecular and cellular mechanisms of spastin in neural development and disease (Review).International journal of molecular medicine · 2021Review
- Review
- Current Knowledge of Endolysosomal and Autophagy Defects in Hereditary Spastic Paraplegia.Cells · 2021Review
- Interorganelle communication, aging, and neurodegeneration.Genes & development · 2021Review
- Lipid Droplets in the Pathogenesis of Hereditary Spastic Paraplegia.Frontiers in molecular biosciences · 2021Review
- The ESCRTs - converging on mechanism.Journal of cell science · 2020Review
- Suppression ofFrontiers in neuroscience · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The hereditary spastic paraplegias (HSPs) are genetic motor neuron diseases characterized by progressive degeneration of corticospinal tract axons. Mutations in SPAST, encoding the microtubule-severing ATPase spastin, are the most common causes of HSP. The broad SPAST mutational spectrum indicates a haploinsufficiency pathogenic mechanism in most cases. Most missense mutations cluster in the ATPase domain, where they disrupt the protein's ability to sever microtubules. However, several putative missense mutations in the protein's microtubule interacting and trafficking (MIT) domain have also been described, but the pathogenicity of these mutations has not been verified with functional studies. Spastin promotes endosomal tubule fission, and defects in this lead to lysosomal enzyme mistrafficking and downstream lysosomal abnormalities. We investigated the function of three disease-associated spastin MIT mutants and found that none was able to promote normal endosomal tubule fission, lysosomal enzyme receptor trafficking, or lysosomal morphology. One of the mutations affected recruitment of spastin to endosomes, a property that requires the canonical function of the MIT domain in binding endosomal sorting complex required for transport (ESCRT)-III proteins. However, the other mutants did not affect spastin's endosomal recruitment, raising the possibility of pathologically important non-canonical roles for the MIT domain. In conclusion, we demonstrate that spastin MIT mutants cause functional abnormalities related to the pathogenesis of HSP. These mutations do not directly affect spastin's microtubule-severing capacity, and so we identify a new molecular pathological mechanism by which spastin mutations may cause disease.
Indexed as
Identifiers
What OpenQuestion holds
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.