ArticleProceedings of the National Academy of Sciences of the United States of America2023
Rab3 mediates a pathway for endocytic sorting and plasma membrane recycling of ordered microdomains.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 31 citations in OpenAlex.
- Structural and functional modifications of neuronal lipid rafts: implications for HIV-associated neurological disorders.Journal of neuroinflammation · 2026Article
- ER exit sites mediated by the COPII adaptor sec24D selectively recruit lipid raft-preferring proteins for rapid ER export.Nature communications · 2025Article
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- Clinical insight-driven micron-sized cholesterol oxidation platform for membrane lipid therapy of advanced ovarian cancer.Journal of nanobiotechnology · 2025Article
- Loss of lipid asymmetry facilitates plasma membrane blebbing by decreasing membrane lipid packing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- RAB-10 cooperates with EHBP-1 to capture vesicular carriers during post-Golgi exocytic trafficking.The Journal of cell biology · 2025Article
- Article
- Tumorigenic and tumoricidal properties of exosomes in cancers; a forward look.Cell communication and signaling : CCS · 2024Review
- tsCRISPR based identification of Rab proteins required for the recycling ofFrontiers in cell and developmental biology · 2024Article
- The Membrane-Mediated Interaction of Liquid-Ordered Lipid Domains in the Presence of Amphipathic Peptides.Membranes · 2023Article
- Compromised Myelin and Axonal Molecular Organization Following Adult-Onset Sulfatide Depletion.Biomedicines · 2023Article
- Lipid rafts, Rab GTPases, and a late endosomal checkpoint for plasma membrane recycling.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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7 authors at 1 institution in 1 country.
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Abstract
The composition of the plasma membrane (PM) must be tightly controlled despite constant, rapid endocytosis, which requires active, selective recycling of endocytosed membrane components. For many proteins, the mechanisms, pathways, and determinants of this PM recycling remain unknown. We report that association with ordered, lipid-driven membrane microdomains (known as rafts) is sufficient for PM localization of a subset of transmembrane proteins and that abrogation of raft association disrupts their trafficking and leads to degradation in lysosomes. Using orthogonal, genetically encoded probes with tunable raft partitioning, we screened for the trafficking machinery required for efficient recycling of engineered microdomain-associated cargo from endosomes to the PM. Using this screen, we identified the Rab3 family as an important mediator of PM localization of microdomain-associated proteins. Disruption of Rab3 reduced PM localization of raft probes and led to their accumulation in Rab7-positive endosomes, suggesting inefficient recycling. Abrogation of Rab3 function also mislocalized the endogenous raft-associated protein Linker for Activation of T cells (LAT), leading to its intracellular accumulation and reduced T cell activation. These findings reveal a key role for lipid-driven microdomains in endocytic traffic and suggest Rab3 as a mediator of microdomain recycling and PM composition.
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