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Drebrin

Review of drebrin

Discovery of drebrin

Drebrin was discovered in 1985 by our group as a unique protein of which expression is transiently up-regulated in parallel with brain development. Since then, we purified drebrin protein, raised antibody against drebrin and cloned drebrin cDNA. Further we showed that drebrin is a unique actin-binding protein which is concentrated at dendritic spines. Please find the history of drebrin discovery in the reference list at early ages.

Drebrin and Neuronal Devedlopment

Drebrin plays a pivotal role in neuonal development (neurite growth and the growth cone shapes).

 develpment1-E

 

Drebrin and Synapse Maturation

In paralell with further maturaion of neurons, drebrin isoform changes from enbryonic form (drebrin E) to adult neuron-specific form (drebrin A). The up-regulation of drebrin A facilitates the formation of dendritic spines.

development2

 In the mature neurons, drebrin A is specifically accumulated at dendritc spines. Interestingly the accumualtion of drebrin A depends on the synaptic activity, and LTP stimulation induce the transient exodus of dreb rin A from dendritic spines. As we see later, drebrin makes stable actin filaments; therefore the transient disappearance of drebrin from dendritic spines play a pivotal role for forming dynamic actin filaments, resulting in the morphological palstic change of dendritic spines.

 LTP-E

 

 

 

 

 In addition to the morphological synaptic plasticity, drebrin also plays a pivotal role of hoemostatic plasticity of the accumualtion of NMDA receptors at dendritic spines.

Drebrin and Dimentia (Alzheimer's disease etc.)

In 1996 we reported that massive disappearance of  drebrin from neuropil occurs in the dimentia disorder such as Alzheimer's disease. This observation is consistent with the idea that persistent loss of drebrin from dendritic spines mayresult in the synaptic dysfunction. Furthermore this idea has been independently confirmed by various groups in the world using postmortem brain, animal model and cultured neurons. In addition it has been reportted that the cognitive function is quantitatively well correlated with the drebrin level in human brain.

dimentia3dimentia

 

 Structure of drebrin molecule and drebrin-binding actin filament

Drebrin has ADF-H domain at N-terminal region, forming superfamily with cofilin and twinfilin. Drebrin is classified into two isoform groups: adult isoform (drebrin A, neuron-specific isoform) and embryonic isoform (drebrin E). Drebrin is reported to bound to various proteins, the most typical and important binding partner is an actin filament. Drebrin bounds to actin filaments and modify the helix pitch of actin polymers, resulting in the decrease of tread milling speed.

Drebrin-imaging-based evaluation of mature synapses

 Drebrin plays a pivotal role in the formation of stable actin filaments in dendritic spines via decreasing the treadmill speed of actin filaments and increasing the helix pitch of actin filaments. The appearance of stable actin filaments in the core of dendritic spines is a marker of the mature synapse enabling synaptic plasticity. We are proposing that the accumulation of drebrin at dendritic spines is a good surrogate marker of the stable actin appearance in dendritic spines. This method is called DIBES (Drebrin-imaging-based evaluation of mature synapses), and are widely used for the screening of the effect of various chemical on neuronal synapses.

 Abe-ta-e

Recent Reviews

  • Shirao T, Gonzalez-Billault C. "Actin filaments and microtubules in dendritic spines." J Neurochem. 126: 155-164 (2013)
  • Cingolani LA, Goda Y. "Actin in action: the interplay between the actin cytoskeleton and synaptic efficacy."Nat Rev Neurosci. 2008 May;9(5):344-56.
  • Sekino Y, Kojima N, Shirao T. “Role of actin cytoskeleton in dendritic spine morphogenesis” Neurochem. Int. 51: 92-104 (2007)  Most cited review paper for drebrin.
  • Kojima, N., Shirao, T. “Synaptic dysfunction and disruption of the postsynaptic drebrin-actin complex: the study of neurological disorders accompanied by cognitive deficits.” Neurosci. Res. 58:1-5 (2007)
  • About Drebrin Antibody

    Recent references in which drebrin immunostaing are used

    Available antibodies against drebrin

    Name of antibodyspecies specificitycommercially availableraised animal
    M2F6noneMBLmouse monoclonal
    M2D6noneonly available from the Shirao laboratorymouse monoclonal
    M2H1noneonly available from the Shirao laboratorymouse monoclonal
    M2E6chickenonly available from the Shirao laboratorymouse monoclonal
    M2A6chickenonly available from the Shirao laboratorymouse monoclonal
    DAS2mouse, rat, humanIBLrabbit polycolnal

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