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The mechanochemistry of endocytosis.

Liu J, Sun Y, Drubin DG, Oster GF - PLoS Biol. (2009)

Bottom Line: Although individual molecular players have been studied intensively, how they all fit into a coherent picture of endocytosis remains unclear.The central idea is that membrane curvature is coupled to the accompanying biochemical reactions.Calculated phase diagrams reproduce endocytic mutant phenotypes observed in experiments and predict unique testable endocytic phenotypes in yeast and mammalian cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, United States of America.

ABSTRACT
Endocytic vesicle formation is a complex process that couples sequential protein recruitment and lipid modifications with dramatic shape transformations of the plasma membrane. Although individual molecular players have been studied intensively, how they all fit into a coherent picture of endocytosis remains unclear. That is, how the proper temporal and spatial coordination of endocytic events is achieved and what drives vesicle scission are not known. Drawing upon detailed knowledge from experiments in yeast, we develop the first integrated mechanochemical model that quantitatively recapitulates the temporal and spatial progression of endocytic events leading to vesicle scission. The central idea is that membrane curvature is coupled to the accompanying biochemical reactions. This coupling ensures that the process is robust and culminates in an interfacial force that pinches off the vesicle. Calculated phase diagrams reproduce endocytic mutant phenotypes observed in experiments and predict unique testable endocytic phenotypes in yeast and mammalian cells. The combination of experiments and theory in this work suggest a unified mechanism for endocytic vesicle formation across eukaryotes.

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Schematics comparing endocytosis in yeast and mammalian cells.(A) Model for yeast endocytosis. (B) Model for mammalian endocytosis (see text).
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pbio-1000204-g007: Schematics comparing endocytosis in yeast and mammalian cells.(A) Model for yeast endocytosis. (B) Model for mammalian endocytosis (see text).

Mentions: Endocytosis in budding yeast evolves in a sequence of events that are explained by the model (as schematized in Figure 7A). As PIP2 accumulates at the endocytic site, it recruits coat proteins to the bud region that nucleate actin polymerization. Using anchorage to the coat proteins (e.g., Sla2), F-actin polymerization and myosin motor activity generate a pulling force that deforms the membrane into a tubule. The high curvature of the tubule in turn recruits BDPs that coat the tubule by binding to PIP2. The BDPs protect the PIP2 along the tubule from hydrolysis by the phosphatase. The coat proteins on the vesicle bud do not protect the PIP2 from hydrolysis as effectively, so a boundary region is created that develops a circumferential interfacial tension. This tension exerts a squeezing force on the phase boundary, which further increases the curvature at the bud neck, which in turn increases the hydrolysis there. Thus a positive feedback loop arises between membrane curvature and PIP2 hydrolysis rates at the interface, the result of which is the rapid growth of the interfacial force leading to vesicle scission (Figure 5). Furthermore, the positive feedback loop between the curvature-sensing and deforming activities of the BDPs ensures rapid turnover of the BDPs, facilitating timely vesicle scission. After scission, PIP2 is hydrolyzed all over the membrane surface, promoting disassembly of the entire endocytic apparatus. Therefore, it is the two intertwined positive feedback loops (Figure 4) that ensure rapid, robust, and timely endocytosis in budding yeast.


The mechanochemistry of endocytosis.

Liu J, Sun Y, Drubin DG, Oster GF - PLoS Biol. (2009)

Schematics comparing endocytosis in yeast and mammalian cells.(A) Model for yeast endocytosis. (B) Model for mammalian endocytosis (see text).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2742711&req=5

pbio-1000204-g007: Schematics comparing endocytosis in yeast and mammalian cells.(A) Model for yeast endocytosis. (B) Model for mammalian endocytosis (see text).
Mentions: Endocytosis in budding yeast evolves in a sequence of events that are explained by the model (as schematized in Figure 7A). As PIP2 accumulates at the endocytic site, it recruits coat proteins to the bud region that nucleate actin polymerization. Using anchorage to the coat proteins (e.g., Sla2), F-actin polymerization and myosin motor activity generate a pulling force that deforms the membrane into a tubule. The high curvature of the tubule in turn recruits BDPs that coat the tubule by binding to PIP2. The BDPs protect the PIP2 along the tubule from hydrolysis by the phosphatase. The coat proteins on the vesicle bud do not protect the PIP2 from hydrolysis as effectively, so a boundary region is created that develops a circumferential interfacial tension. This tension exerts a squeezing force on the phase boundary, which further increases the curvature at the bud neck, which in turn increases the hydrolysis there. Thus a positive feedback loop arises between membrane curvature and PIP2 hydrolysis rates at the interface, the result of which is the rapid growth of the interfacial force leading to vesicle scission (Figure 5). Furthermore, the positive feedback loop between the curvature-sensing and deforming activities of the BDPs ensures rapid turnover of the BDPs, facilitating timely vesicle scission. After scission, PIP2 is hydrolyzed all over the membrane surface, promoting disassembly of the entire endocytic apparatus. Therefore, it is the two intertwined positive feedback loops (Figure 4) that ensure rapid, robust, and timely endocytosis in budding yeast.

Bottom Line: Although individual molecular players have been studied intensively, how they all fit into a coherent picture of endocytosis remains unclear.The central idea is that membrane curvature is coupled to the accompanying biochemical reactions.Calculated phase diagrams reproduce endocytic mutant phenotypes observed in experiments and predict unique testable endocytic phenotypes in yeast and mammalian cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular and Cell Biology, University of California Berkeley, Berkeley, California, United States of America.

ABSTRACT
Endocytic vesicle formation is a complex process that couples sequential protein recruitment and lipid modifications with dramatic shape transformations of the plasma membrane. Although individual molecular players have been studied intensively, how they all fit into a coherent picture of endocytosis remains unclear. That is, how the proper temporal and spatial coordination of endocytic events is achieved and what drives vesicle scission are not known. Drawing upon detailed knowledge from experiments in yeast, we develop the first integrated mechanochemical model that quantitatively recapitulates the temporal and spatial progression of endocytic events leading to vesicle scission. The central idea is that membrane curvature is coupled to the accompanying biochemical reactions. This coupling ensures that the process is robust and culminates in an interfacial force that pinches off the vesicle. Calculated phase diagrams reproduce endocytic mutant phenotypes observed in experiments and predict unique testable endocytic phenotypes in yeast and mammalian cells. The combination of experiments and theory in this work suggest a unified mechanism for endocytic vesicle formation across eukaryotes.

Show MeSH
Related in: MedlinePlus