Spatiotemporal proteomics reveals the biosynthetic lysosomal membrane protein interactome in neurons
Year: 2024
Type: article
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.
Source: Nature Communications
Institutions: Utrecht University, Vrije Universiteit Amsterdam
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,790
Awards: The role of the endoplasmic reticulum in shaping the axonal proteome in health and disease, Secretion, Autophagy and their role in Neurodegeneration, Unravelling the regulatory mechanisms for lysosome formation and aggregate clearance in neurons, G434337789, Uncovering the machinery for the sorting of newly synthesized proteins into the axon
OpenAlex ID: W4408003072