Determinants of endocytic membrane geometry, stability, and scission

Kishimoto, Tadamitsu; Sun, Yidi; Buser, Christopher; Liu, Jian; Michelot, Alphée; Drubin, David G.

doi:10.1073/pnas.1113413108

Cited by 81 publications

(126 citation statements)

References 80 publications

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“…1 and Fig. S1), in line with inferences drawn from experimental work (17). Contrary to the prevailing picture of BARs on membranes, in our simulations the proteins initially aggregate in the areas of negative Gaussian curvature, i.e., in troughs.…”

Section: Resultssupporting

confidence: 64%

“…In the mechanism of clathrin-mediated endocytosis, different BARs are thought to be recruited at different times, assembling at the early stages, coating the emerging tubule, and participating in membrane fission (16,17). Considering that deletion of many of these proteins often shows only moderate consequences on the membrane morphology, it reinforces the argument that the remodeling is a result of robust interactions between proteins and the surface of the membrane.…”

mentioning

confidence: 52%

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Linear aggregation of proteins on the membrane as a prelude to membrane remodeling

Šimunović

Srivastava

Voth

2013

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

146

185

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Adhesion and insertion of curvature-mediating proteins can induce dramatic structural changes in cell membranes, allowing them to participate in several key cellular tasks. The way proteins interact to generate curvature remains largely unclear, especially at early stages of membrane remodeling. Using a coarse-grained model of Bin/ amphiphysin/Rvs domain with an N-terminal helix (N-BAR) interacting with flat membranes and vesicles, we demonstrate that at low protein surface densities, binding of N-BAR domain proteins to the membrane is followed by a linear aggregation and the formation of meshes on the surface. In this process, the proteins assemble at the base of emerging membrane buds. Our work shows that beyond a more straightforward scaffolding mechanism at high bound densities, the interplay of anisotropic interactions and the local stress imposed by the N-BAR proteins results in deep invaginations and endocytic vesicular bud-like deformations, an order of magnitude larger than the size of the individual protein. Our results imply that by virtue of this mechanism, cell membranes may achieve rapid local increases in protein concentration.coarse-grained simulation | membrane stress | self-assembly | membrane curvature | Gaussian curvature L ipid membranes protect cells and their organelles and serve as mechanical support for proteins involved in signal transduction and cellular trafficking (1). Owing to the way lipids are assembled into bilayers of mesoscopic length and molecular width, membranes behave as elastic and highly dynamic molecular sheets. Their innate multiscale nature is further evident in the local interplay between proteins and lipids, which results in large-scale membrane remodeling characterized by an impressive array of morphologies (2). These properties allow biological membranes to take part in several important cellular processes, as their restructuring is key to enabling communication between cells, formation of organelles, trafficking, division, and cell migration (1).The interactions between individual proteins and lipid molecules alone are insufficient to remodel flat membrane sheets to an appreciable extent, implying that the experimentally observed membrane remodeling is a result of the concerted action of multiple proteins (3) in ways mechanistically differing from the mode of action of a single protein. Considering the multiple timescales required to capture protein dynamics as the membrane deformations are induced, as well as the difficulty in separating individual events of the remodeling process, this mechanism remains largely unclear. It previously was demonstrated that the binding of curvature-inducing nanoparticles may form tubular and vesicular structures, in which particles interact with one another solely via curvature (3-6). Furthermore, analytical theory predicts that anisotropic inclusions may induce budding on the membrane surface (7). However, the way proteins assemble on the membrane and how their oligomerization couples to both local and long-wavelength transformat...

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Section: Resultssupporting

confidence: 64%

mentioning

confidence: 52%

Linear aggregation of proteins on the membrane as a prelude to membrane remodeling

Šimunović

Srivastava

Voth

2013

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

146

185

View full text Add to dashboard Cite

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“…In yeast cells, clathrin, actin, and BAR proteins contribute to vesicle formation in different capacities. Though the inhibition of actin polymerization completely arrests endocytosis (9,11,12,14), the absence of clathrin and BAR proteins only leads to ∼50% and 25% reduction in the internalization events, respectively (14)(15)(16)(17)(18). Although a high scission rate is maintained in BAR mutant cells, there is a fundamental difference between the shape evolution process in these and the wild-type cells.…”

Section: Bar Proteinsmentioning

confidence: 92%

“…A higher tension in a membrane makes a membrane taut and harder to bend, thus increasing the energetic cost required to form new vesicles. As a consequence, in cells experiencing high membrane tension, such as yeast cells and mammalian cells with polarized domains or those subjected to increased tension, actin dynamics has been found to be necessary to provide additional driving force to successfully complete CME (8)(9)(10)(11)(12)(13)(14). Although this fact has been established by seminal experimental studies, how actin forces actually drive vesicle formation and facilitate vesicle scission is not well understood.…”

Section: Bar Proteinsmentioning

confidence: 92%

Endocytic proteins drive vesicle growth via instability in high membrane tension environment

Walani

Torres

Agrawal

2015

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

101

152

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Clathrin-mediated endocytosis (CME) is a key pathway for transporting cargo into cells via membrane vesicles; it plays an integral role in nutrient import, signal transduction, neurotransmission, and cellular entry of pathogens and drug-carrying nanoparticles. Because CME entails substantial local remodeling of the plasma membrane, the presence of membrane tension offers resistance to bending and hence, vesicle formation. Experiments show that in such high-tension conditions, actin dynamics is required to carry out CME successfully. In this study, we build on these pioneering experimental studies to provide fundamental mechanistic insights into the roles of two key endocytic proteins-namely, actin and BAR proteins-in driving vesicle formation in high membrane tension environment. Our study reveals an actin force-induced "snapthrough instability" that triggers a rapid shape transition from a shallow invagination to a highly invaginated tubular structure. We show that the association of BAR proteins stabilizes vesicles and induces a milder instability. In addition, we present a rather counterintuitive role of BAR depolymerization in regulating the shape evolution of vesicles. We show that the dissociation of BAR proteins, supported by actin-BAR synergy, leads to considerable elongation and squeezing of vesicles. Going beyond the membrane geometry, we put forth a stress-based perspective for the onset of vesicle scission and predict the shapes and composition of detached vesicles. We present the snap-through transition and the high in-plane stress as possible explanations for the intriguing direct transformation of broad and shallow invaginations into detached vesicles in BAR mutant yeast cells.clathrin-mediated endocytosis | membrane tension | instability | actin | BAR proteins

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“…Finally, there are apparently striking differences in the mechanism of membrane scission in mammalian and yeast cells. In mammalian cells, membrane scission absolutely requires the large GTPase dynamin (Ferguson and De Camilli 2012) whereas in yeast cells actin, rather than an equivalent GTPase is important for scission (Kishimoto et al 2011). The mechanistic similarities and differences between mammalian and yeast endocytosis are summarized in Figure 1.…”

Section: Endocytic Accessory Factors and Regulation Of Cmementioning

confidence: 99%