ArticleMolecular biology of the cell2007
Canonical interaction of cyclin G associated kinase with adaptor protein 1 regulates lysosomal enzyme sorting.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 citations in OpenAlex.
- Cyclin-G-associated kinase modifies α-synuclein expression levels and toxicity in Parkinson's disease: results from the GenePD Study.Human molecular genetics · 2011Pooled it
- Genomewide association study for onset age in Parkinson disease.BMC medical genetics · 2009Pooled it
- Low-frequency genetic variants in GAK enhance Golgi function and protect against Parkinson's disease.medRxiv : the preprint server for health sciences · 2025Article
- Article
- Chemo-small extracellular vesicles released in cisplatin-resistance ovarian cancer cells are regulated by the lysosomal function.Journal of extracellular biology · 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
- GAK and PRKCD are positive regulators of PRKN-independent mitophagy.Nature communications · 2021Article
- Targeted disruption of GAK stagnates autophagic flux by disturbing lysosomal dynamics.International journal of molecular medicine · 2021Article
- Investigating the role of the transcriptional regulator Ure2 on the metabolism of Saccharomyces cerevisiae: a multi-omics approach.Applied microbiology and biotechnology · 2021Article
- The multifaceted role of kinases in amyotrophic lateral sclerosis: genetic, pathological and therapeutic implications.Brain : a journal of neurology · 2020Review
- Dynamics of Auxilin 1 and GAK in clathrin-mediated traffic.The Journal of cell biology · 2020Article
- Chemical genetic identification of GAK substrates reveals its role in regulating NaLife science alliance · 2018Article
- A new hypothesis for Parkinson's disease pathogenesis: GTPase-p38 MAPK signaling and autophagy as convergence points of etiology and genomics.Molecular neurodegeneration · 2018Review
- Comparative Protein Interaction Network Analysis Identifies Shared and Distinct Functions for the Human ROCO Proteins.Proteomics · 2018Article
- Article
- Monitoring the Targeting of Cathepsin D to the Lysosome by Metabolic Labeling and Pulse-chase Analysis.Bio-protocol · 2017Article
- Oral Treatment with the Ghrelin Receptor Agonist HM01 Attenuates Cachexia in Mice Bearing Colon-26 (C26) Tumors.International journal of molecular sciences · 2017Article
- The Potential Mutation of GAK Gene in the Typical Sporadic Parkinson's Disease from the Han Population of Chinese Mainland.Molecular neurobiology · 2016Article
- Genes associated with Parkinson's disease: regulation of autophagy and beyond.Journal of neurochemistry · 2016Review
- Bivalent Motif-Ear Interactions Mediate the Association of the Accessory Protein Tepsin with the AP-4 Adaptor Complex.The Journal of biological chemistry · 2015Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
The adaptor protein 1 (AP1) complex is a heterotetramer that participates in cargo sorting into clathrin-coated vesicles at the trans-Golgi network (TGN) and endosomes. The gamma subunit of AP1 possesses a C-terminal "ear" domain that recruits a cohort of accessory proteins through recognition of a shared canonical motif, PsiG[PDE][PsiLM] (where Psi is an aromatic residue). The physiological relevance of these ear-motif interactions, however, remains to be demonstrated. Here we report that the cyclin G-associated kinase (GAK) has two sequences fitting this motif, FGPL and FGEF, which mediate binding to the AP1-gamma-ear domain in vitro. Mutation of both gamma-ear-binding sequences or depletion of AP1-gamma by RNA interference (RNAi) decreases the association of GAK with the TGN in vivo. Depletion of GAK by RNAi impairs the sorting of the acid hydrolase, cathepsin D, to lysosomes. Importantly, expression of RNAi-resistant GAK restores the lysosomal sorting of cathepsin D in cells depleted of endogenous GAK, whereas expression of a similar construct bearing mutations in both gamma-ear-binding sequences fails to correct the sorting defect. Thus, interactions between the PsiG[PDE][PsiLM]-motif sequences in GAK and the AP1-gamma-ear domain are critical for the recruitment of GAK to the TGN and the function of GAK in lysosomal enzyme sorting.
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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.