The FTS-Hook-FHIP (FHF) complex interacts with AP-4 to mediate perinuclear distribution of AP-4 and its cargo ATG9A
| Autor: | Juan S. Bonifacino, Xuefeng Ren, Rafael Mattera, Chad D. Williamson |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Protein subunit
Adaptor Protein Complex 4 Vesicular Transport Proteins Autophagy-Related Proteins Biology Microtubules Microtubule Cell Line Tumor Organelle Humans Molecular Biology Spastic Paraplegia Hereditary Autophagy Signal transducing adaptor protein HOOK1 Dyneins Membrane Proteins Cell Biology Articles Transmembrane protein Cell biology Protein Transport FHF complex HEK293 Cells Membrane Trafficking HeLa Cells trans-Golgi Network |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | The heterotetrameric adaptor protein complex 4 (AP-4) is a component of a protein coat associated with the trans-Golgi network (TGN). Mutations in AP-4 subunits cause a complicated form of autosomal-recessive hereditary spastic paraplegia termed AP-4-deficiency syndrome. Recent studies showed that AP-4 mediates export of the transmembrane autophagy protein ATG9A from the TGN to preautophagosomal structures. To identify additional proteins that cooperate with AP-4 in ATG9A trafficking, we performed affinity purification-mass spectrometry followed by validation of the hits by biochemical and functional analyses. This approach resulted in the identification of the fused toes homolog-Hook-FHIP (FHF) complex as a novel AP-4 accessory factor. We found that the AP-4-FHF interaction is mediated by direct binding of the AP-4 μ4 subunit to coiled-coil domains in the Hook1 and Hook2 subunits of FHF. Knockdown of FHF subunits resulted in dispersal of AP-4 and ATG9A from the perinuclear region of the cell, consistent with the previously demonstrated role of the FHF complex in coupling organelles to the microtubule (MT) retrograde motor dynein-dynactin. These findings thus uncover an additional mechanism for the distribution of ATG9A within cells and provide further evidence for a role of protein coats in coupling transport vesicles to MT motors. |
| Databáze: | OpenAIRE |
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