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Updated: Jun 11, 2025

Reconstitution of Msp1 Extraction Activity with Fully Purified Components
Published on: August 10, 2021
BLTP3A is associated with membranes of the late endocytic pathway and is an effector of CASM
Michael G Hanna1,2,3,4,5, Hely O Rodriguez Cruz1,2,3,4,5, Kenshiro Fujise1,2,3,4,5
1Department of Neuroscience, Yale University School of Medicine, New Haven, CT.
Abstract:
Recent studies have identified a family of rod-shaped proteins thought to mediate lipid transfer at intracellular membrane contacts by a bridge-like mechanism. We show one such protein, bridge-like lipid transfer protein 3A (BLTP3A)/UHRF1BP1 binds VAMP7 vesicles via its C-terminal region and anchors them to lysosomes via its chorein domain containing N-terminal region to Rab7. Upon lysosome damage, BLTP3A-positive vesicles rapidly (within minutes) dissociate from lysosomes. Lysosome damage is known to activate the CASM (Conjugation of ATG8 to Single Membranes) pathway leading to lipidation and recruitment to lysosomes of mammalian ATG8 (mATG8) proteins. We find that this process drives the reassociation of BLTP3A with damaged lysosomes via an interaction of its LIR motif with mATG8 which coincides with a dissociation from the vesicles. Our findings reveal that BLTP3A is an effector of CASM, potentially as part of a mechanism to help repair or minimize lysosome damage.
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