ArticleAutophagy2019
ZFYVE26/SPASTIZIN and SPG11/SPATACSIN mutations in hereditary spastic paraplegia types AR-SPG15 and AR-SPG11 have different effects on autophagy and endocytosis.
Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Pooled it
- Miglustat does not impact clinical progression in patients with spastic paraplegia type 11.Neurogenetics · 2025Trial
- Hereditary spastic paraplegia (HSP) gene 11 (Spg11) attenuates lipid accumulation in myeloid cells and neuroinflammation in the midbrain without affecting α-synuclein pathology.Journal of neuroinflammation · 2026Article
- Maspardin/SPG21 controls lysosome motility and TFEB phosphorylation through RAB7 positioning.The Journal of cell biology · 2026Article
- Structural basis for membrane remodeling by the AP5-SPG11-SPG15 complex.Nature structural & molecular biology · 2025Article
- Microglia and CD8+ T cell activation precede neuronal loss in a murine model of spastic paraplegia 15.The Journal of experimental medicine · 2025Article
- A competition network connects Rab5 and Rab11 GTPases at the surface of endocytic structures.iScience · 2025Article
- A Novel Crossover between Vici Syndrome and Spastic Paraplegia: Variant of EPG5 in Spastic Paraplegia.Indian journal of pediatrics · 2025Article
- Axon demyelination and degeneration in a zebrafishOpen biology · 2024Article
- Genetic heterogeneity in epilepsy and comorbidities: insights from Pakistani families.BMC neurology · 2024Article
- Lysosomes as coordinators of cellular catabolism, metabolic signalling and organ physiology.Nature reviews. Molecular cell biology · 2024Review
- Neuroinflammatory disease signatures in SPG11-related hereditary spastic paraplegia patients.Acta neuropathologica · 2024Article
- Orchestrating vesicular and nonvesicular membrane dynamics by intrinsically disordered proteins.EMBO reports · 2023Review
- Article
- Autophagic lysosome reformation in health and disease.Autophagy · 2023Review
- Rescue of lysosomal function as therapeutic strategy for SPG15 hereditary spastic paraplegia.Brain : a journal of neurology · 2023Article
- Lunapark deficiency leads to an autosomal recessive neurodevelopmental phenotype with a degenerative course, epilepsy and distinct brain anomalies.Brain communications · 2023Article
- Case report: Hereditary spastic paraplegia with a novel homozygous mutation inFrontiers in neurology · 2023Article
- Ubap1 knock-in mice reproduced the phenotype of SPG80.Journal of human genetics · 2022Article
- Endosome maturation links PI3Kα signaling to lysosome repopulation during basal autophagy.The EMBO journal · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ZFYVE26/Spastizin and SPG11/Spatacsin encode 2 large proteins that are mutated in hereditary autosomal-recessive spastic paraplegia/paraparesis (HSP) type 15 (AR-SPG15) and type 11 (AR-SPG11), respectively. We previously have reported that AR-SPG15-related ZFYVE26 mutations lead to autophagy defects with accumulation of immature autophagosomes. ZFYVE26 and SPG11 were found to be part of a complex including the AP5 (adaptor related protein complex 5) and to have a critical role in autophagic lysosomal reformation with identification of autophagic and lysosomal defects in cells with both AR-SPG15- and AR-SPG11-related mutations. In spite of these similarities between the 2 proteins, here we report that ZFYVE26 and SPG11 are differently involved in autophagy and endocytosis. We found that both ZFYVE26 and SPG11 interact with RAB5A and RAB11, 2 proteins regulating endosome trafficking and maturation, but only ZFYVE26 mutations affected RAB protein interactions and activation. ZFYVE26 mutations lead to defects in the fusion between autophagosomes and endosomes, while SPG11 mutations do not affect this step and lead to a milder autophagy defect. We thus demonstrate that ZFYVE26 and SPG11 affect the same cellular physiological processes, albeit at different levels: both proteins have a role in autophagic lysosome reformation, but only ZFYVE26 acts at the intersection between endocytosis and autophagy, thus representing a key player in these 2 processes. Indeed expression of the constitutively active form of RAB5A in cells with AR-SPG15-related mutations partially rescues the autophagy defect. Finally the model we propose demonstrates that autophagy and the endolysosomal pathway are central processes in the pathogenesis of these complicated forms of hereditary spastic paraparesis. Abbreviations: ALR, autophagic lysosome reformation; AP5, adaptor related protein complex 5; AR, autosomal-recessive; HSP, hereditary spastic paraplegia/paraparesis; ATG14, autophagy related 14; BafA, bafilomycin A
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