The pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission

Dar, Srishti; Pucadyil, Thomas J.

doi:10.1091/mbc.e16-09-0640

Cited by 26 publications

(45 citation statements)

References 46 publications

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“…While it may be that classical dynamins are facilitators of scission in higher eukaryotic cells, other PH‐less family members may be able to effect scission reactions, at least on certain lipid templates: the templates used in this particular study contained 25 mol% cardiolipin, which may be easier to fragment, for example, than a mitochondrial outer membrane. Consistently, a dynamin where the PH domain is replaced with a stretch of 6 histidines or lysines can still be recruited to anionic lipid templates and can constrict and sever them, in the context of supported bilayers with excess membrane reservoir . However, the lifetimes of individual constricted helices are significantly extended, which results in a decrease in overall rates of fission.…”

Section: Dynamin's Dirty Laundry and Remaining Challengesmentioning

confidence: 99%

“…Consistently, a dynamin where the PH domain is replaced with a stretch of 6 histidines or lysines can still be recruited to anionic lipid templates and can constrict and sever them, in the context of supported bilayers with excess membrane reservoir. 124 However, the lifetimes of individual constricted helices are significantly extended, which results in a decrease in overall rates of fission. Hence, at least using this membrane model, the PH domain may be a catalytic enhancer.…”

Section: Does a Ph Domain Make A Fission Dynamin?mentioning

confidence: 99%

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The structural biology of the dynamin‐related proteins: New insights into a diverse, multitalented family

Ford

Chappie

2019

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Dynamin‐related proteins are multidomain, mechanochemical GTPases that self‐assemble and orchestrate a wide array of cellular processes. Over the past decade, structural insights from X‐ray crystallography and cryo‐electron microscopy have reshaped our mechanistic understanding of these proteins. Here, we provide a historical perspective on these advances that highlights the structural attributes of different dynamin family members and explores how these characteristics affect GTP hydrolysis, conformational coupling and oligomerization. We also discuss a number of lingering challenges remaining in the field that suggest future directions of study.

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Section: Dynamin's Dirty Laundry and Remaining Challengesmentioning

confidence: 99%

Section: Does a Ph Domain Make A Fission Dynamin?mentioning

confidence: 99%

The structural biology of the dynamin‐related proteins: New insights into a diverse, multitalented family

Ford

Chappie

2019

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“…Nevertheless, dynamin's membrane fission activity requires input of chemical energy in the form of GTP (10)(11)(12)(13). Cycles of GTP hydrolysis in dynamin oligomers have the effect of constricting the membrane neck, consistent with dynamin's role in promoting fission; yet, the mechanics of this process remain unclear (1,10,(14)(15)(16)(17)(18)(19). The most constricted state of dynamin, observed for a transition statedefective mutant, is associated with apparent tilting of the membrane binding pleckstrin homology (PH) domains (9).…”

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confidence: 99%

The tilted helix model of dynamin oligomers

Kadosh

Colom

Yellin

et al. 2019

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

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Dynamin proteins assemble into characteristic helical structures around necks of clathrin-coated membrane buds. Hydrolysis of dynamin-bound GTP results in both fission of the membrane neck and partial disruption of the dynamin oligomer. Imaging by atomic force microscopy reveals that, on GTP hydrolysis, dynamin oligomers undergo a dynamic remodeling and lose their distinctive helical shape. While breakup of the dynamin helix is a critical stage in clathrin-mediated endocytosis, the mechanism for this remodeling of the oligomer has not been resolved. In this paper, we formulate an analytical, elasticity-based model for the reshaping and disassembly of the dynamin scaffold. We predict that the shape of the oligomer is modulated by the orientation of dynamin’s pleckstrin homology (PH) domain relative to the underlying membrane. Our results indicate that tilt of the PH domain drives deformation and fragmentation of the oligomer, in agreement with experimental observations. This model motivated the introduction of the tilted helix: a curve that maintains a fixed angle between its normal and the normal of the embedding surface. Our findings highlight the importance of tilt as a key regulator of size and morphology of membrane-bound oligomers.

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“…The excess membrane allows for membrane remodelling processes to occur in the presence of the solid support and be monitored by fluorescence and electron microscopy. These supported membranes have been successfully used to reveal the physical basis of membrane remodelling promoted by protein crowding 97 or performed by endocytic [98][99][100][101] and autophagic proteins 102 . Similarly, the supported membrane tubes (SMrT) 103 are synthetic membranes mimicking membrane tethers pulled by proteins 104,105 that can be used to study the impact of local curvature on protein-membrane interactions 101 .…”

Section: Engineering Curved Membranes To Understand the Mechanisms Ofmentioning

confidence: 99%

Topography design in model membranes: Where biology meets physics

Chand

Beales

Claeyssens

et al. 2018

Exp Biol Med (Maywood)

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Phospholipid membranes are necessary for the compartmentalisation of chemistries within biological cells and for initiation and propagation of cell signalling. The morphological and chemical complexity of cellular membranes represent a challenge for dissecting the biochemical processes occurring at these interfaces. Therefore, investigations of the biological events occurring at the membrane require suitable models able to reproduce the complexities of this surface. Solid-supported lipid bilayers (SLB) are simplified physical replicas of biological membranes that allow the bottom-up reconstruction of the molecular mechanisms occurring at cellular interfaces. In this brief review we introduce how the properties of SLBs can be tuned to mimic biological membranes, highlighting the engineering approaches for creating spatially resolved patterns of lipid bilayers and supported membranes with curved geometries. Additionally, we present how SLBs have 2 ! been employed to reconstitute the biophysical basis of molecular mechanisms involved in intercellular signalling and more recently, membrane trafficking. KeywordsSolid-supported lipid bilayers, membrane patterning, membrane curvature, synthetic biology, in vitro reconstitution. Impact StatementArtificial membranes with complex topography aid the understanding of biological processes where membrane geometry plays a key regulatory role. In this review, we highlight how emerging material and engineering technologies have been employed to create minimal models of cell signalling pathways, in vitro. These artificial systems allow life scientists to answer ever more challenging questions in regards to mechanisms in cellular biology. In vitro reconstitution of biology is an area that draws on the expertise and collaboration between biophysicists, material scientists and biologists and has recently generated a number of high impact results, some of which are also discussed in this review.

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The pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission

Cited by 26 publications

References 46 publications

The structural biology of the dynamin‐related proteins: New insights into a diverse, multitalented family

The structural biology of the dynamin‐related proteins: New insights into a diverse, multitalented family

The tilted helix model of dynamin oligomers

Topography design in model membranes: Where biology meets physics

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