ArticleInternational journal of molecular medicine2021
Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics.
Article in International journal of molecular medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Activation of the endocytosis pathway stratifies subtypes and therapeutic sensitivity in colorectal cancer.Research square · 2026Article
- Phosphoproteomic profiling reveals post-translational dysregulation in Huntington's disease patient-derived neurons.Cellular & molecular biology letters · 2026Article
- GAK antagonises ROCK-dependent regulation of actomyosin dynamics.Journal of cell science · 2026Article
- Bayesian inference of genetic pleiotropy identifies drug targets and repurposable medicines for human complex diseases.medRxiv : the preprint server for health sciences · 2025Article
- Article
- Methamphetamine Increases Tubulo-Vesicular Areas While Dissipating Proteins from Vesicles Involved in Cell Clearance.International journal of molecular sciences · 2024Article
- Joint-tissue integrative analysis identifies high-risk genes for Parkinson's disease.Frontiers in neuroscience · 2024Article
- Cyclin-G-associated kinase GAK/dAux regulates autophagy initiation via ULK1/Atg1 in glia.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Autophagic lysosome reformation in health and disease.Autophagy · 2023Review
- Selective dopaminergic vulnerability in Parkinson's disease: new insights into the role of DAT.Frontiers in neuroscience · 2023Review
- Autophagy and neurodegeneration: Unraveling the role of C9ORF72 in the regulation of autophagy and its relationship to ALS-FTD pathology.Frontiers in cellular neuroscience · 2023Review
- Article
- Crosstalk of organelles in Parkinson's disease - MiT family transcription factors as central players in signaling pathways connecting mitochondria and lysosomes.Molecular neurodegeneration · 2022Review
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Authors and funding
9 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The autophagy‑lysosome system allows cells to adapt to environmental changes by regulating the degradation and recycling of cellular components, and to maintain homeostasis by removing aggregated proteins and defective organelles. Cyclin G‑associated kinase (GAK) is involved in the regulation of clathrin‑dependent endocytosis and cell cycle progression. In addition, a single nucleotide polymorphism at the GAK locus has been reported as a risk factor for Parkinson's disease. However, the roles of GAK in the autophagy‑lysosome system are not completely understood, thus the present study aimed to clarify this. In the present study, under genetic disruption or chemical inhibition of GAK, analyzing autophagic flux and observing morphological changes of autophagosomes and autolysosomes revealed that GAK controlled lysosomal dynamics via actomyosin regulation, resulting in a steady progression of autophagy. GAK knockout (KO) in A549 cells impaired autophagosome‑lysosome fusion and autophagic lysosome reformation, which resulted in the accumulation of enlarged autophagosomes and autolysosomes during prolonged starvation. The stagnation of autophagic flux accompanied by these phenomena was also observed with the addition of a GAK inhibitor. Furthermore, the addition of Rho‑associated protein kinase (ROCK) inhibitor or ROCK1 knockdown mitigated GAK KO‑mediated effects. The results suggested a vital role of GAK in controlling lysosomal dynamics via maintaining lysosomal homeostasis during autophagy.
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