Spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons
Abstract Lysosomes are membrane-bound organelles critical for maintaining cellular homeostasis. Delivery of biosynthetic lysosomal proteins to lysosomes is crucial to orchestrate proper lysosomal function. However, it remains unknown how the delivery of biosynthetic lysosomal proteins to lysosomes i...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55052-w |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849766499977265152 |
|---|---|
| author | Chun Hei Li Noortje Kersten Nazmiye Özkan Dan T. M. Nguyen Max Koppers Harm Post Maarten Altelaar Ginny G. Farias |
| author_facet | Chun Hei Li Noortje Kersten Nazmiye Özkan Dan T. M. Nguyen Max Koppers Harm Post Maarten Altelaar Ginny G. Farias |
| author_sort | Chun Hei Li |
| collection | DOAJ |
| description | Abstract Lysosomes are membrane-bound organelles critical for maintaining cellular homeostasis. Delivery of biosynthetic lysosomal proteins to lysosomes is crucial to orchestrate proper lysosomal function. However, it remains unknown how the delivery of biosynthetic lysosomal proteins to lysosomes is ensured in neurons, which are highly polarized cells. Here, we developed Protein Origin, Trafficking And Targeting to Organelle Mapping (POTATOMap), by combining trafficking synchronization and proximity-labelling based proteomics, to unravel the trafficking routes and interactome of the biosynthetic lysosomal membrane protein LAMP1 at specified time points. This approach, combined with advanced microscopy, enables us to identify the neuronal domain-specific trafficking machineries of biosynthetic LAMP1. We reveal a role in replenishing axonal lysosomes, in delivery of newly synthesized axonal synaptic proteins, and interactions with RNA granules to facilitate hitchhiking in the axon. POTATOMap offers a robust approach to map out dynamic biosynthetic protein trafficking and interactome from their origin to destination. |
| format | Article |
| id | doaj-art-0ccba86d7a0e4a858050ec3fde324a57 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-0ccba86d7a0e4a858050ec3fde324a572025-08-20T03:04:34ZengNature PortfolioNature Communications2041-17232024-12-0115111910.1038/s41467-024-55052-wSpatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neuronsChun Hei Li0Noortje Kersten1Nazmiye Özkan2Dan T. M. Nguyen3Max Koppers4Harm Post5Maarten Altelaar6Ginny G. Farias7Cell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht UniversityCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht UniversityCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht UniversityCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht UniversityCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht UniversityBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht UniversityBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht UniversityCell Biology, Neurobiology and Biophysics, Department of Biology, Faculty of Science, Utrecht UniversityAbstract Lysosomes are membrane-bound organelles critical for maintaining cellular homeostasis. Delivery of biosynthetic lysosomal proteins to lysosomes is crucial to orchestrate proper lysosomal function. However, it remains unknown how the delivery of biosynthetic lysosomal proteins to lysosomes is ensured in neurons, which are highly polarized cells. Here, we developed Protein Origin, Trafficking And Targeting to Organelle Mapping (POTATOMap), by combining trafficking synchronization and proximity-labelling based proteomics, to unravel the trafficking routes and interactome of the biosynthetic lysosomal membrane protein LAMP1 at specified time points. This approach, combined with advanced microscopy, enables us to identify the neuronal domain-specific trafficking machineries of biosynthetic LAMP1. We reveal a role in replenishing axonal lysosomes, in delivery of newly synthesized axonal synaptic proteins, and interactions with RNA granules to facilitate hitchhiking in the axon. POTATOMap offers a robust approach to map out dynamic biosynthetic protein trafficking and interactome from their origin to destination.https://doi.org/10.1038/s41467-024-55052-w |
| spellingShingle | Chun Hei Li Noortje Kersten Nazmiye Özkan Dan T. M. Nguyen Max Koppers Harm Post Maarten Altelaar Ginny G. Farias Spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons Nature Communications |
| title | Spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons |
| title_full | Spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons |
| title_fullStr | Spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons |
| title_full_unstemmed | Spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons |
| title_short | Spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons |
| title_sort | spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons |
| url | https://doi.org/10.1038/s41467-024-55052-w |
| work_keys_str_mv | AT chunheili spatiotemporalproteomicsrevealsthebiosyntheticlysosomalmembraneproteininteractomeinneurons AT noortjekersten spatiotemporalproteomicsrevealsthebiosyntheticlysosomalmembraneproteininteractomeinneurons AT nazmiyeozkan spatiotemporalproteomicsrevealsthebiosyntheticlysosomalmembraneproteininteractomeinneurons AT dantmnguyen spatiotemporalproteomicsrevealsthebiosyntheticlysosomalmembraneproteininteractomeinneurons AT maxkoppers spatiotemporalproteomicsrevealsthebiosyntheticlysosomalmembraneproteininteractomeinneurons AT harmpost spatiotemporalproteomicsrevealsthebiosyntheticlysosomalmembraneproteininteractomeinneurons AT maartenaltelaar spatiotemporalproteomicsrevealsthebiosyntheticlysosomalmembraneproteininteractomeinneurons AT ginnygfarias spatiotemporalproteomicsrevealsthebiosyntheticlysosomalmembraneproteininteractomeinneurons |