Drebrin-induced Stabilization of Actin Filaments*

Background: Drebrin is a mammalian neuronal protein that binds to and organizes filamentous actin (F-actin) in dendritic spines. Results: Drebrin protects actin filaments from depolymerization and rescues their formation in different cases of longitudinal and lateral contact perturbation. Conclusion: Drebrin stabilizes actin filaments through its effect on their interstrand and intrastrand contacts. Significance: We elucidate the mechanism by which drebrin governs F-actin dynamics in dendritic spines. Drebrin is a mammalian neuronal protein that binds to and organizes filamentous actin (F-actin) in dendritic spines, the receptive regions of most excitatory synapses that play a crucial role in higher brain functions. Here, the structural effects of drebrin on F-actin were examined in solution. Depolymerization and differential scanning calorimetry assays show that F-actin is stabilized by the binding of drebrin. Drebrin inhibits depolymerization mainly at the barbed end of F-actin. Full-length drebrin and its C-terminal truncated constructs were used to clarify the domain requirements for these effects. The actin binding domain of drebrin decreases the intrastrand disulfide cross-linking of Cys-41 (in the DNase I binding loop) to Cys-374 (C-terminal) but increases the interstrand disulfide cross-linking of Cys-265 (hydrophobic loop) to Cys-374 in the yeast mutants Q41C and S265C, respectively. We also demonstrate, using solution biochemistry methods and EM, the rescue of filament formation by drebrin in different cases of longitudinal interprotomer contact perturbation: the T203C/C374S yeast actin mutant and grimelysin-cleaved skeletal actin (between Gly-42 and Val-43). Additionally, we show that drebrin rescues the polymerization of V266G/L267G, a hydrophobic loop yeast actin mutant with an impaired lateral interface formation between the two filament strands. Overall, our data suggest that drebrin stabilizes actin filaments through its effect on their interstrand and intrastrand contacts.

• Publication year

  2013

• Venue

  Journal of Biological Chemistry

• Publication date

  2013-05-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M113.472647PMID 23696644PMCID PMC3707693
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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• The role of the drebrin/EB3/Cdk5 pathway in dendritic spine plasticity, implications for Alzheimer’s disease.

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