Bridge-like lipid transfer protein 3A (BLTP3A) is associated with membranes of the late endocytic pathway and is an effector of CASM.

Autor: Hanna MG; Department of Neuroscience, Yale University School of Medicine, New Haven, CT.; Department of Cell Biology, Yale University School of Medicine, New Haven, CT.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT.; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD., Rodriguez Cruz HO; Department of Neuroscience, Yale University School of Medicine, New Haven, CT.; Department of Cell Biology, Yale University School of Medicine, New Haven, CT.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT.; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD., Fujise K; Department of Neuroscience, Yale University School of Medicine, New Haven, CT.; Department of Cell Biology, Yale University School of Medicine, New Haven, CT.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT.; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD., Li Z; Proteomics Core Facility, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY., Monetti M; Proteomics Core Facility, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY., De Camilli P; Department of Neuroscience, Yale University School of Medicine, New Haven, CT.; Department of Cell Biology, Yale University School of Medicine, New Haven, CT.; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT.; Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT.; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD.
Jazyk: angličtina
Zdroj: BioRxiv : the preprint server for biology [bioRxiv] 2024 Sep 28. Date of Electronic Publication: 2024 Sep 28.
DOI: 10.1101/2024.09.28.615015
Abstrakt: Recent studies have identified a family of rod-shaped proteins which includes VPS13 and ATG2 and are thought to mediate unidirectional lipid transport at intracellular membrane contacts by a bridge-like mechanism. Here, we show that one such protein, BLTP3A/UHRF1BP1, associates with VAMP7-positive vesicles via its C-terminal region and anchors them to lysosomes via the binding of its chorein domain containing N-terminal region to Rab7. Upon damage of lysosomal membranes and resulting mATG8 recruitment to their surface by CASM, BLTP3A first dissociates from lysosomes but then reassociates with them via an interaction of its LIR motif with mATG8. Such interaction is mutually exclusive to the binding of BLTP3A to vesicles and leaves its N-terminal chorein domain, i.e. the proposed entry site of lipids into this family of proteins, available for binding to another membrane, possibly the ER. Our findings reveal that BLTP3A is an effector CASM, potentially as part of a mechanism to help repair or minimize lysosome damage by delivering lipids.
Databáze: MEDLINE
Externí odkaz: