The active zone protein Clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagy
Autophagy is essential for cellular homeostasis and function. In neurons, autophagosome biogenesis is temporally and spatially regulated to occur near presynaptic sites, in part via the trafficking of autophagy transmembrane protein ATG-9. The molecules that regulate autophagy by sorting ATG-9 at sy...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2023-04-01
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| Series: | PLoS Biology |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101500/?tool=EBI |
| _version_ | 1797846133070888960 |
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| author | Zhao Xuan Sisi Yang Benjamin Clark Sarah E. Hill Laura Manning Daniel A. Colón-Ramos |
| author_facet | Zhao Xuan Sisi Yang Benjamin Clark Sarah E. Hill Laura Manning Daniel A. Colón-Ramos |
| author_sort | Zhao Xuan |
| collection | DOAJ |
| description | Autophagy is essential for cellular homeostasis and function. In neurons, autophagosome biogenesis is temporally and spatially regulated to occur near presynaptic sites, in part via the trafficking of autophagy transmembrane protein ATG-9. The molecules that regulate autophagy by sorting ATG-9 at synapses remain largely unknown. Here, we conduct forward genetic screens at single synapses of C. elegans neurons and identify a role for the long isoform of the active zone protein Clarinet (CLA-1L) in regulating sorting of autophagy protein ATG-9 at synapses, and presynaptic autophagy. We determine that disrupting CLA-1L results in abnormal accumulation of ATG-9 containing vesicles enriched with clathrin. The ATG-9 phenotype in cla-1(L) mutants is not observed for other synaptic vesicle proteins, suggesting distinct mechanisms that regulate sorting of ATG-9-containing vesicles and synaptic vesicles. Through genetic analyses, we uncover the adaptor protein complexes that genetically interact with CLA-1 in ATG-9 sorting. We also determine that CLA-1L extends from the active zone to the periactive zone and genetically interacts with periactive zone proteins in ATG-9 sorting. Our findings reveal novel roles for active zone proteins in the sorting of ATG-9 and in presynaptic autophagy. Autophagosome biogenesis is temporally and spatially regulated to occur near presynaptic sites in neurons. This study identifies novel roles for active zone proteins in specifically regulating activity-dependent presynaptic autophagy via sorting of the autophagy protein ATG-9. |
| first_indexed | 2024-04-09T17:51:04Z |
| format | Article |
| id | doaj.art-0ebfbaa926e142f7827ef25d5ac6c635 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-04-09T17:51:04Z |
| publishDate | 2023-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-0ebfbaa926e142f7827ef25d5ac6c6352023-04-16T05:31:14ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852023-04-01214The active zone protein Clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagyZhao XuanSisi YangBenjamin ClarkSarah E. HillLaura ManningDaniel A. Colón-RamosAutophagy is essential for cellular homeostasis and function. In neurons, autophagosome biogenesis is temporally and spatially regulated to occur near presynaptic sites, in part via the trafficking of autophagy transmembrane protein ATG-9. The molecules that regulate autophagy by sorting ATG-9 at synapses remain largely unknown. Here, we conduct forward genetic screens at single synapses of C. elegans neurons and identify a role for the long isoform of the active zone protein Clarinet (CLA-1L) in regulating sorting of autophagy protein ATG-9 at synapses, and presynaptic autophagy. We determine that disrupting CLA-1L results in abnormal accumulation of ATG-9 containing vesicles enriched with clathrin. The ATG-9 phenotype in cla-1(L) mutants is not observed for other synaptic vesicle proteins, suggesting distinct mechanisms that regulate sorting of ATG-9-containing vesicles and synaptic vesicles. Through genetic analyses, we uncover the adaptor protein complexes that genetically interact with CLA-1 in ATG-9 sorting. We also determine that CLA-1L extends from the active zone to the periactive zone and genetically interacts with periactive zone proteins in ATG-9 sorting. Our findings reveal novel roles for active zone proteins in the sorting of ATG-9 and in presynaptic autophagy. Autophagosome biogenesis is temporally and spatially regulated to occur near presynaptic sites in neurons. This study identifies novel roles for active zone proteins in specifically regulating activity-dependent presynaptic autophagy via sorting of the autophagy protein ATG-9.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101500/?tool=EBI |
| spellingShingle | Zhao Xuan Sisi Yang Benjamin Clark Sarah E. Hill Laura Manning Daniel A. Colón-Ramos The active zone protein Clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagy PLoS Biology |
| title | The active zone protein Clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagy |
| title_full | The active zone protein Clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagy |
| title_fullStr | The active zone protein Clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagy |
| title_full_unstemmed | The active zone protein Clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagy |
| title_short | The active zone protein Clarinet regulates synaptic sorting of ATG-9 and presynaptic autophagy |
| title_sort | active zone protein clarinet regulates synaptic sorting of atg 9 and presynaptic autophagy |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10101500/?tool=EBI |
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