Molecular Cooperativity of Drebrin1-300 Binding and Structural Remodeling of F-Actin

Sharma, Shivani; Grintsevich, Elena E.; Hsueh, Carlin; Reisler, Emil; Gimzewski, James K.

doi:10.1016/j.bpj.2012.06.006

Cited by 35 publications

(43 citation statements)

References 30 publications

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“…However, the molecular mechanism of such displacement/competition is not immediately evident. Cooperative binding to actin filaments was documented for both cofilin and drebrin A [Cao et al, ; Sharma et al, ]. Also, we showed recently the opposite effects of these two proteins on F‐actin morphology: cofilin was shown to shorten the helical pitch of actin filaments and drebrin caused an increase in the length of their helical repeats [McGough et al, ; Sharma et al, ].…”

Section: Introductionmentioning

confidence: 67%

“…Also, we showed recently the opposite effects of these two proteins on F‐actin morphology: cofilin was shown to shorten the helical pitch of actin filaments and drebrin caused an increase in the length of their helical repeats [McGough et al, ; Sharma et al, ]. Moreover, the propagation of these morphological changes to undecorated filament regions was documented for drebrin by atomic force microscopy (AFM) imaging [Sharma et al, ] and was proposed for cofilin based on differential scanning calorimetry (DSC), fluorescence, and cross‐linking assays [Bobkov et al, ]. Such long range effects can underlie non‐competitive (allosteric) inhibition of drebrin‐F‐actin interaction by cofilin (as was previously reported for Arp2/3 complex [Chan et al, ]), and vice versa.…”

Section: Introductionmentioning

confidence: 99%

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Drebrin inhibits cofilin‐induced severing of F‐actin

Grintsevich

Reisler

2014

Cytoskeleton

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Molecular cross-talk between neuronal drebrin A and cofilin is believed to be a part of the activity-dependent cytoskeleton-modulating pathway in dendritic spines. Impairments in this pathway are implicated also in synaptic dysfunction in Alzheimer’s disease, Down syndrome, epilepsy, and normal aging. However, up to now the molecular interplay between cofilin and drebrin has not been elucidated. TIRF microscopy and solution experiments revealed that full length drebrin A or its actin binding core (Drb1-300) inhibits, but do not abolish cofilin-induced severing of actin filaments. Cosedimentation experiments showed that F-actin can be fully occupied with combination of these two proteins. The dependence of cofilin binding on fractional saturation of actin filaments with drebrin suggests direct competition between these two proteins for F-actin binding. This implies that cofilin and drebrin can either overcome or reverse the allosteric changes in F-actin induced by the competitor’s binding. The ability of cofilin to displace drebrin from actin filaments is pH dependent and is facilitated at acidic pH (6.8). Pre-steady state kinetic experiments reveal that both binding and dissociation of drebrin to/from actin filaments is faster than that reported for cooperative binding of cofilin. We found, that drebrin displacement by cofilin is greatly inhibited when actin severing is abolished, which might be linked to the cooperativity of drebrin binding to actin filaments. Our results contribute to molecular understanding of the competitive interactions of drebrin and cofilin with actin filaments.

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Section: Introductionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Drebrin inhibits cofilin‐induced severing of F‐actin

Grintsevich

Reisler

2014

Cytoskeleton

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“…Namely, drebrin interaction with F‐actin shows cooperativity (Sharma et al . ). In addition to the morphological change, drebrin significantly decreases the rate of F‐actin depolymerization (Mikati et al .…”

Section: Genetic and Biochemical Properties Of Drebrinmentioning

confidence: 97%

The role of drebrin in neurons

Shirao

Hanamura

Koganezawa

et al. 2017

Journal of Neurochemistry

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Drebrin is an actin-binding protein that changes the helical pitch of actin filaments (F-actin), and drebrin-decorated F-actin shows slow treadmilling and decreased rate of depolymerization. Moreover, the characteristic morphology of drebrindecorated F-actin enables it to respond differently to the same signals from other actin cytoskeletons. Drebrin consists of two major isoforms, drebrin E and drebrin A. In the developing brain, drebrin E appears in migrating neurons and accumulates in the growth cones of axons and dendrites. Drebrin E-decorated Factin links lamellipodium F-actin to microtubules in the growth cones. Then drebrin A appears at nascent synapses and drebrin A-decorated F-actin facilitates postsynaptic molecular assembly. In the adult brain, drebrin A-decorated F-actin is concentrated in the central region of dendritic spines. During long-term potentiation initiation, NMDA receptor-mediated Ca 2+ influx induces the transient exodus of drebrin A-decorated F-actin via myosin II ATPase activation. Because of the unique physical characteristics of drebrin A-decorated F-actin, this exodus likely contributes to the facilitation of F-actin polymerization and spine enlargement. Additionally, drebrin reaccumulation in dendritic spines is observed after the exodus. In our drebrin exodus model of structure-based synaptic plasticity, reestablishment of drebrin A-decorated F-actin is necessary to keep the enlarged spine size during long-term potentiation maintenance. In this review, we introduce the genetic and biochemical properties of drebrin and the roles of drebrin in early stage of brain development, synaptic formation and synaptic plasticity. Further, we discuss the pathological relevance of drebrin loss in Alzheimer's disease.

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“…55 The previous successes of tapping mode AFM imaging in unraveling the structure and mechanics of F-actin–ABP (actin binding protein) complexes 32,56 prompted us to apply this technique to seek the single-filament level structure of INF2-FFC and F-actin assembly at the nanoscale level. Figure 4 shows a typical AFM tapping mode image of a 1:1 ratio of INF2-FFC and F-actin complexes revealing a ringlike arrangement of formin FH2 homodimers encircled around actin filaments (Figure 4a,b).…”

Section: Resultsmentioning

confidence: 99%

Nanostructured Self-Assembly of Inverted Formin 2 (INF2) and F-Actin–INF2 Complexes Revealed by Atomic Force Microscopy

et al. 2014

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Self-organization of cytoskeletal proteins such as actin and tubulin into filaments and microtubules is frequently assisted by the proteins binding to them. Formins are regulatory proteins that nucleate the formation of new filaments and are essential for a wide range of cellular functions. The vertebrate inverted formin 2 (INF2) has both actin filament nucleating and severing/depolymerizing activities connected to its ability to encircle actin filaments. Using atomic force microscopy, we report that a formin homology 2 (FH2) domain-containing construct of INF2 (INF2-FH1-FH2-C or INF2-FFC) self-assembles into nanoscale ringlike oligomeric structures in the absence of actin filaments, demonstrating an inherent ability to reorganize from a dimeric to an oligomeric state. A construct lacking the C-terminal region (INF2-FH1-FH2 or INF2-FF) also oligomerizes, confirming the dominant role of FH2-mediated interactions. Moreover, INF2-FFC domains were observed to organize into ringlike structures around single actin filaments. This is the first demonstration that formin FH2 domains can self-assemble into oligomers in the absence of filaments and has important implications for observing unaveraged decoration and/or remodeling of filaments by actin binding proteins.

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Molecular Cooperativity of Drebrin1-300 Binding and Structural Remodeling of F-Actin

Cited by 35 publications

References 30 publications

Drebrin inhibits cofilin‐induced severing of F‐actin

Drebrin inhibits cofilin‐induced severing of F‐actin

The role of drebrin in neurons

Nanostructured Self-Assembly of Inverted Formin 2 (INF2) and F-Actin–INF2 Complexes Revealed by Atomic Force Microscopy

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