Building endocytic pits without clathrin

Johannes, Ludger; Parton, Robert G.; Bassereau, Patricia; Mayor, Satyajit

doi:10.1038/nrm3968

Cited by 189 publications

(223 citation statements)

References 130 publications

Supporting

Mentioning

216

Contrasting

Order By: Relevance

“…The mechanism that we have uncovered coordinates different endocytic pathways to bring together a ligand-receptor pair and facilitate their interaction in the low pH environment of the endosome. Although the existence of different modes of endocytosis have been known (21,75), this study provides a step toward understanding their interplay in vivo. This could be a general principle, applicable in many contexts where fine-tuning the signal is important.…”

Section: Discussionmentioning

confidence: 99%

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

Hemalatha

Prabhakara

Mayor

2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

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

show abstract

Section: Discussionmentioning

confidence: 99%

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

Hemalatha

Prabhakara

Mayor

2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Understanding such functional links and their bearing on the membrane dynamics will naturally allow us to probe the properties of the membrane domains GPI-anchored protein's form at the cell surface and how such domains can be endocytosed ( 126 ). Addressing this will necessitate better assays to relate the local composition of the membrane milieu to the clustering of GPI-anchored proteins.…”

Section: Future Directions and Perspectivementioning

confidence: 99%

GPI-anchored protein organization and dynamics at the cell surface

Saha

Anilkumar

Mayor

2016

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

of the protein called glycosylphosphatidylinositol (GPI)-anchored proteins. The basic structure of a GPI-anchored protein consists of phosphatidylinositol (PI) linked to an unusual non-N -acetyl glucosamine, which, in turn, is linked to three mannose residues followed by an ethanolamine covalently linked to the protein via an amide linkage (EtNP-6Man ␣ 1-2Man ␣ 1-6Man ␣ 1-4GlcN ␣ 1-6 myo inositolphospholipid, Fig. 1A ). Depending on the species and functional context, there may exist variations in the side chain associated with the glycan core. These have been summarized in ( 1 ). The lipid moiety is necessary for the incorporation of GPI-anchored proteins into so-called lipid rafts/microdomains ( 2, 3 ), which can serve as a sorting station for a number of cell signaling molecules, thereby functioning as a reaction center. GPI-anchored proteins can exist in different forms depending on the context and the tissue in which they are expressed. Alternate splicing can cause the same protein to exhibit TM, soluble, or GPI-anchored forms; for example, neural cell adhesion molecule (NCAM) can exist in its GPI-anchored and soluble form when expressed in muscles; whereas, it takes up a TM form instead of the soluble form in brain. GPI anchoring of proteins occurs at the luminal face of The plasma membrane of the cell is comprised of a diverse set of proteins, many of which are transmembrane (TM) proteins spanning the entire bilayer, but a significant proportion of proteins are also lipid tethered, containing a complex glycan core attached to the C terminus

show abstract

“…STxB enters cells by clathrin-independent endocytosis (reviewed in Johannes et al, 2015) in a process that is operated in tight association with the BAR domain protein endophilin-A2 (endoA2, also known as SH3GL1) (Renard et al, 2015), which also functions in the clathrin-independent uptake processes of endogenous cellular proteins . In HeLa cells that stably expressed an endoA2-GFP fusion protein, we observed that STxB-ss-saporin colocalized as efficiently as STxB with endoA2 at the plasma membrane and in very early uptake intermediates (supplementary material Fig.…”

Section: Internalization and Retrograde Trafficking Of Stxb-saporin Cmentioning

confidence: 99%

Retrograde transport is not required for cytosolic translocation of the B-subunit of Shiga toxin

García-Castillo

Tran

Bobard

et al. 2015

Journal of Cell Science

Self Cite

View full text Add to dashboard Cite

Antigen-presenting cells have the remarkable capacity to transfer exogenous antigens to the cytosol for processing by proteasomes and subsequent presentation on major histocompatibility complex class-I (MHC-I) molecules, a process termed cross-presentation. This is the target of biomedical approaches that aim to trigger a therapeutic immune response. The receptor-binding B-subunit of Shiga toxin (STxB) has been developed as an antigen delivery tool for such immunotherapy applications. In this study, we have analyzed pathways and trafficking factors that are involved in this process. A covalent conjugate between STxB and saporin was generated to quantitatively sample the membrane translocation step to the cytosol in differentiated monocyte-derived THP-1 cells. We have found that retrograde trafficking to the Golgi complex was not required for STxBsaporin translocation to the cytosol or for STxB-dependent antigen cross-presentation. Depletion of endosomal Rab7 inhibited, and lowering membrane cholesterol levels favored STxB-saporin translocation. Interestingly, experiments with reducible and nonreducible linker-arm-STxB conjugates led to the conclusion that after translocation, STxB remains associated with the cytosolic membrane leaflet. In summary, we report new facets of the endosomal escape process bearing relevance to antigen cross-presentation.

show abstract

Building endocytic pits without clathrin

Cited by 189 publications

References 130 publications

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

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

GPI-anchored protein organization and dynamics at the cell surface

Retrograde transport is not required for cytosolic translocation of the B-subunit of Shiga toxin

Contact Info

Product

Resources

About