Actin Dynamics Drive Membrane Reorganization and Scission in Clathrin-Independent Endocytosis

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128

161

Significance Entry of bacteria into host cells critically depends on their proper engulfment by the plasma membrane. So far, actin polymerization has been described as a major driving force in this process. However, our study reveals that the interaction of the bacterial surface lectin LecA with the host cell glycosphingolipid Gb3 is fully sufficient to promote engulfment of Pseudomonas aeruginosa , whereas actin polymerization is dispensable. Hence, the formation of a “lipid zipper” represents a previously unidentified mechanism of bacterial uptake and demonstrates that bacterial pathogens have evolved lipid-based invasion strategies that may function in addition to protein receptor-based ones. Furthermore, by identifying the LecA/Gb3 interaction as the major invasion-promoting factor, our study provides new targets for drugs that may prevent bacterial invasion and dissemination.

Section: Discussionmentioning

confidence: 97%

A lipid zipper triggers bacterial invasion

Eierhoff

Bastian

Thuenauer

et al. 2014

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128

161

“…This finding argues for a very prominent role of GPIanchored HSPGs in recruiting Wg to the cell surface, as well as for its endocytosis. Some clathrin and dynamin-independent pathway cargoes drive their own endocytosis when concentrated on the plasma membrane by different binders (57,58). A similar mechanism can be envisioned for Wg endocytosis via CG pathway, with HSPGs aiding in clustering of Wg at the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

Endocytosis of Wingless via a dynamin-independent pathway is necessary for signaling in Drosophila wing discs

Hemalatha

Prabhakara

Mayor

2016

Endocytosis of ligand-receptor complexes regulates signal transduction during development. In particular, clathrin and dynamin-dependent endocytosis has been well studied in the context of patterning of the Drosophila wing disc, wherein apically secreted Wingless (Wg) encounters its receptor, DFrizzled2 (DFz2), resulting in a distinctive dorso-ventral pattern of signaling outputs. Here, we directly track the endocytosis of Wg and DFz2 in the wing disc and demonstrate that Wg is endocytosed from the apical surface devoid of DFz2 via a dynamin-independent CLIC/GEEC pathway, regulated by Arf1, Garz, and class I PI3K. Subsequently, Wg containing CLIC/GEEC endosomes fuse with DFz2-containing vesicles derived from the clathrin and dynamin-dependent endocytic pathway, which results in a low pH-dependent transfer of Wg to DFz2 within the merged and acidified endosome to initiate Wg signaling. The employment of two distinct endocytic pathways exemplifies a mechanism wherein cells in tissues leverage multiple endocytic pathways to spatially regulate signaling.clathrin and dynamin-independent endocytosis | Wingless signaling | pH of endosome | wing disc development | Garz localization

“…Such actin polymerization has been proposed to increase local membrane tension and/or strain at lipid domain boundary regions (line tension), processes thought to promote membrane fission (69)(70)(71). Alternatively, actin polymerization has also been proposed to stabilize membrane buds or tubules, allowing time for cargo loading (73).…”

Section: Discussionmentioning

confidence: 99%

“…Local actin polymerization is associated with many membranebudding processes (69)(70)(71)(72). Such actin polymerization has been proposed to increase local membrane tension and/or strain at lipid domain boundary regions (line tension), processes thought to promote membrane fission (69)(70)(71).…”

Section: Discussionmentioning

confidence: 99%

A TOCA/CDC-42/PAR/WAVE functional module required for retrograde endocytic recycling

Bai

Grant

2015

Endosome-to-Golgi transport is required for the function of many key membrane proteins and lipids, including signaling receptors, small-molecule transporters, and adhesion proteins. The retromer complex is well-known for its role in cargo sorting and vesicle budding from early endosomes, in most cases leading to cargo fusion with the trans-Golgi network (TGN). Transport from recycling endosomes to the TGN has also been reported, but much less is understood about the molecules that mediate this transport step. Here we provide evidence that the F-BAR domain proteins TOCA-1 and TOCA-2 (Transducer of Cdc42 dependent actin assembly), the small GTPase CDC-42 (Cell division control protein 42), associated polarity proteins PAR-6 (Partitioning defective 6) and PKC-3/atypical protein kinase C, and the WAVE actin nucleation complex mediate the transport of MIG-14/Wls and TGN-38/TGN38 cargo proteins from the recycling endosome to the TGN in Caenorhabditis elegans. Our results indicate that CDC-42, the TOCA proteins, and the WAVE component WVE-1 are enriched on RME-1-positive recycling endosomes in the intestine, unlike retromer components that act on early endosomes. Furthermore, we find that retrograde cargo TGN-38 is trapped in early endosomes after depletion of SNX-3 (a retromer component) but is mainly trapped in recycling endosomes after depletion of CDC-42, indicating that the CDC-42-associated complex functions after retromer in a distinct organelle. Thus, we identify a group of interacting proteins that mediate retrograde recycling, and link these proteins to a poorly understood trafficking step, recycling endosome-to-Golgi transport. We also provide evidence for the physiological importance of this pathway in WNT signaling.retromer | endocytic recycling | endosome | toca | wave