ArticleCellular and molecular life sciences : CMLS2020
ESCRT-III-associated proteins and spastin inhibit protrudin-dependent polarised membrane traffic.
Article in Cellular and molecular life sciences : CMLS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 30 citations in OpenAlex.
- Modeling spastic paraplegia 4 with corticospinal motor neuron-enriched cortical organoids reveals genotype-phenotype and HDAC6-targetable pathology.Cell reports · 2026Article
- DeSUMOylation of Spastin Enhances AMPA Receptor Recycling and Synaptic Plasticity via IST1-Dependent Endosomal Sorting.Molecular neurobiology · 2025Article
- Targeting MDM2 affects spastin protein levels and functions: implications for HSP treatment.Cell death discovery · 2025Article
- Article
- Effects of DeSUMOylated Spastin on AMPA Receptor Surface Delivery and Synaptic Function Are Enhanced by Phosphorylating at Ser210.Molecular neurobiology · 2024Article
- IST1 regulates select recycling pathways.Traffic (Copenhagen, Denmark) · 2024Article
- Article
- Phosphorylation mutation impairs the promoting effect of spastin on neurite outgrowth without affecting its microtubule severing ability.European journal of histochemistry : EJH · 2023Article
- Article
- ER as master regulator of membrane trafficking and organelle function.The Journal of cell biology · 2022Review
- Modeling gain-of-function and loss-of-function components of SPAST-based hereditary spastic paraplegia using transgenic mice.Human molecular genetics · 2022Article
- Phosphorylation of Spastin Promotes the Surface Delivery and Synaptic Function of AMPA Receptors.Frontiers in cellular neuroscience · 2022Article
- The Role of Spastin in Axon Biology.Frontiers in cell and developmental biology · 2022Review
- Different fusion tags affect the activity of ubiquitin overexpression on spastin protein stability.European journal of histochemistry : EJH · 2021Article
- Molecular and cellular mechanisms of spastin in neural development and disease (Review).International journal of molecular medicine · 2021Review
- Current Knowledge of Endolysosomal and Autophagy Defects in Hereditary Spastic Paraplegia.Cells · 2021Review
- Final Exon Frameshift BiallelicBrain sciences · 2021Article
- Hereditary Spastic Paraplegia and Future Therapeutic Directions: Beneficial Effects of Small Compounds Acting on Cellular Stress.Frontiers in neuroscience · 2021Review
- Protrudin functions from the endoplasmic reticulum to support axon regeneration in the adult CNS.Nature communications · 2020Article
- Membrane constriction and thinning by sequential ESCRT-III polymerization.Nature structural & molecular biology · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in the gene encoding the microtubule severing ATPase spastin are the most frequent cause of hereditary spastic paraplegia, a genetic condition characterised by length-dependent axonal degeneration. Here, we show that HeLa cells lacking spastin and embryonic fibroblasts from a spastin knock-in mouse model become highly polarised and develop cellular protrusions. In HeLa cells, this phenotype was rescued by wild-type spastin, but not by forms unable to sever microtubules or interact with endosomal ESCRT-III proteins. Cells lacking the spastin-interacting ESCRT-III-associated proteins IST1 or CHMP1B also developed protrusions. The protrusion phenotype required protrudin, a RAB-interacting protein that interacts with spastin and localises to ER-endosome contact sites, where it promotes KIF5-dependent endosomal motility to protrusions. Consistent with this, the protrusion phenotype in cells lacking spastin also required KIF5. Lack or mutation of spastin resulted in functional consequences for receptor traffic of a pathway implicated in HSP, as Bone Morphogenetic Protein receptor distribution became polarised. Our results, therefore, identify a novel role for ESCRT-III proteins and spastin in regulating polarised membrane traffic.
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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.