Multivesicular bodies (MVBs) contain intralumenal vesicles that are delivered to lysosomes for degradation or released extracellularly for intercellular signaling. Here, we identified Caenorhabditis elegans filamin FLN-2 as a novel regulator of MVB biogenesis. FLN-2 co-localizes with V-ATPase subunits on MVBs, and the loss of FLN-2 affects MVB biogenesis, reducing the number of MVBs in C. elegans hypodermis. FLN-2 associates with actin filaments and is required for F-actin organization. Like fln-2(lf) mutation, inactivation of the V0 or V1 sector of V-ATPase or inhibition of actin polymerization impairs MVB biogenesis. Super-resolution imaging shows that FLN-2 docks V-ATPase-decorated MVBs onto actin filaments. FLN-2 interacts via its calponin-homology domains with F-actin and the V1-E subunit, VHA-8. Our data suggest that FLN-2 mediates the docking of MVBs on the actin cytoskeleton, which is required for MVB biogenesis.
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| http://dx.doi.org/10.1083/jcb.202201020 | DOI Listing |
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