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Membrane manipulations by the ESCRT machinery.

Odorizzi G - F1000Res (2015)

Bottom Line: The endosomal sorting complexes required for transport (ESCRTs) collectively comprise a machinery that was first known for its function in the degradation of transmembrane proteins in the endocytic pathway of eukaryotic cells.Since their discovery, however, ESCRTs have been recognized as playing important roles at the plasma membrane, which appears to be the original site of function for the ESCRT machinery.This article reviews some of the major research findings that have shaped our current understanding of how the ESCRT machinery controls membrane dynamics and considers new roles for the ESCRT machinery that might be driven by these mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, USA.

ABSTRACT
The endosomal sorting complexes required for transport (ESCRTs) collectively comprise a machinery that was first known for its function in the degradation of transmembrane proteins in the endocytic pathway of eukaryotic cells. Since their discovery, however, ESCRTs have been recognized as playing important roles at the plasma membrane, which appears to be the original site of function for the ESCRT machinery. This article reviews some of the major research findings that have shaped our current understanding of how the ESCRT machinery controls membrane dynamics and considers new roles for the ESCRT machinery that might be driven by these mechanisms.

No MeSH data available.


Related in: MedlinePlus

Broad overview of endosomal sorting complex required for transport (ESCRT) activities in membrane dynamics.ESCRTs are generally represented by a spiral, which reflects the conformation adopted by ESCRT-III. (A) In the intralumenal vesicle (ILV) budding pathway, ESCRTs sort transmembrane proteins at endosomes into ILVs that are degraded when endosomes fuse with lysosomes. (B) In the viral budding pathway, ESCRTs are required at the plasma membrane (PM) for the release of infectious viral particles. (C) In the abscission step of cytokinesis, ESCRTs are required at the PM for membrane scission that separates dividing cells. (D) In the exosome budding pathway, ILVs created by ESCRTs at endosomes are released into the extracellular environment when endosomes fuse with the PM. (E) In the ectosome budding pathway, extracellular vesicles are released directly from the PM. Recent studies implicate the ESCRT machinery functioning in the repair of PM damage (F) and in the elimination of dysfunctional nuclear pore complex (NPC) intermediates (denoted in red) from the inner nuclear membrane (G).
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f1: Broad overview of endosomal sorting complex required for transport (ESCRT) activities in membrane dynamics.ESCRTs are generally represented by a spiral, which reflects the conformation adopted by ESCRT-III. (A) In the intralumenal vesicle (ILV) budding pathway, ESCRTs sort transmembrane proteins at endosomes into ILVs that are degraded when endosomes fuse with lysosomes. (B) In the viral budding pathway, ESCRTs are required at the plasma membrane (PM) for the release of infectious viral particles. (C) In the abscission step of cytokinesis, ESCRTs are required at the PM for membrane scission that separates dividing cells. (D) In the exosome budding pathway, ILVs created by ESCRTs at endosomes are released into the extracellular environment when endosomes fuse with the PM. (E) In the ectosome budding pathway, extracellular vesicles are released directly from the PM. Recent studies implicate the ESCRT machinery functioning in the repair of PM damage (F) and in the elimination of dysfunctional nuclear pore complex (NPC) intermediates (denoted in red) from the inner nuclear membrane (G).

Mentions: A key insight at the time of its discovery was that the ESCRT-I complex binds ubiquitin4. ESCRT-0 was subsequently found to have the same ubiquitin-binding property7, as was ESCRT-II11. Shortly before the ESCRTs were described as ubiquitin-binding protein complexes, studies revealed that many transmembrane proteins at the plasma membrane are ubiquitinated on their cytosolic domains and that this modification was essential for their degradation at lysosomes12. Together, these observations established that one of the functions of the ESCRT machinery is to target ubiquitinated transmembrane proteins for lysosomal degradation by sorting them at endosomes into ILVs, which then are exposed to degradative hydrolytic enzymes when late endosomes fuse with lysosomes (Figure 1A).


Membrane manipulations by the ESCRT machinery.

Odorizzi G - F1000Res (2015)

Broad overview of endosomal sorting complex required for transport (ESCRT) activities in membrane dynamics.ESCRTs are generally represented by a spiral, which reflects the conformation adopted by ESCRT-III. (A) In the intralumenal vesicle (ILV) budding pathway, ESCRTs sort transmembrane proteins at endosomes into ILVs that are degraded when endosomes fuse with lysosomes. (B) In the viral budding pathway, ESCRTs are required at the plasma membrane (PM) for the release of infectious viral particles. (C) In the abscission step of cytokinesis, ESCRTs are required at the PM for membrane scission that separates dividing cells. (D) In the exosome budding pathway, ILVs created by ESCRTs at endosomes are released into the extracellular environment when endosomes fuse with the PM. (E) In the ectosome budding pathway, extracellular vesicles are released directly from the PM. Recent studies implicate the ESCRT machinery functioning in the repair of PM damage (F) and in the elimination of dysfunctional nuclear pore complex (NPC) intermediates (denoted in red) from the inner nuclear membrane (G).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4544380&req=5

f1: Broad overview of endosomal sorting complex required for transport (ESCRT) activities in membrane dynamics.ESCRTs are generally represented by a spiral, which reflects the conformation adopted by ESCRT-III. (A) In the intralumenal vesicle (ILV) budding pathway, ESCRTs sort transmembrane proteins at endosomes into ILVs that are degraded when endosomes fuse with lysosomes. (B) In the viral budding pathway, ESCRTs are required at the plasma membrane (PM) for the release of infectious viral particles. (C) In the abscission step of cytokinesis, ESCRTs are required at the PM for membrane scission that separates dividing cells. (D) In the exosome budding pathway, ILVs created by ESCRTs at endosomes are released into the extracellular environment when endosomes fuse with the PM. (E) In the ectosome budding pathway, extracellular vesicles are released directly from the PM. Recent studies implicate the ESCRT machinery functioning in the repair of PM damage (F) and in the elimination of dysfunctional nuclear pore complex (NPC) intermediates (denoted in red) from the inner nuclear membrane (G).
Mentions: A key insight at the time of its discovery was that the ESCRT-I complex binds ubiquitin4. ESCRT-0 was subsequently found to have the same ubiquitin-binding property7, as was ESCRT-II11. Shortly before the ESCRTs were described as ubiquitin-binding protein complexes, studies revealed that many transmembrane proteins at the plasma membrane are ubiquitinated on their cytosolic domains and that this modification was essential for their degradation at lysosomes12. Together, these observations established that one of the functions of the ESCRT machinery is to target ubiquitinated transmembrane proteins for lysosomal degradation by sorting them at endosomes into ILVs, which then are exposed to degradative hydrolytic enzymes when late endosomes fuse with lysosomes (Figure 1A).

Bottom Line: The endosomal sorting complexes required for transport (ESCRTs) collectively comprise a machinery that was first known for its function in the degradation of transmembrane proteins in the endocytic pathway of eukaryotic cells.Since their discovery, however, ESCRTs have been recognized as playing important roles at the plasma membrane, which appears to be the original site of function for the ESCRT machinery.This article reviews some of the major research findings that have shaped our current understanding of how the ESCRT machinery controls membrane dynamics and considers new roles for the ESCRT machinery that might be driven by these mechanisms.

View Article: PubMed Central - PubMed

Affiliation: Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, USA.

ABSTRACT
The endosomal sorting complexes required for transport (ESCRTs) collectively comprise a machinery that was first known for its function in the degradation of transmembrane proteins in the endocytic pathway of eukaryotic cells. Since their discovery, however, ESCRTs have been recognized as playing important roles at the plasma membrane, which appears to be the original site of function for the ESCRT machinery. This article reviews some of the major research findings that have shaped our current understanding of how the ESCRT machinery controls membrane dynamics and considers new roles for the ESCRT machinery that might be driven by these mechanisms.

No MeSH data available.


Related in: MedlinePlus