Drebrin

Tomoaki Shirao, Yuko Sekino, Shirao, Tomoaki, Sekino, Yuko

Drebrin was first discovered by our group as "developmentally regulated brain protein" from the chicken optic tectum. Drebrin is an actin-binding protein, which is classified into two major isoforms produced by alternative splicing from a single DBN1 gene. The isoform predominantly expressed in the adult brain (drebrin A) is neuron specific, containing a neuron-specific sequence (Ins2) in the middle of the molecule. Drebrin A is highly concentrated in dendritic spines, and its accumulation level is regulated by synaptic activity. In contrast, drebrin E, which lacks Ins2, is found in widespread but not ubiquitous cell types in various tissues. The isoform conversion from drebrin E to drebrin A occurs in parallel with synaptogenesis. Drebrin decorating F-actin is found at the recipient side of cell-cell communication systems, such as gap junctions, adherens junctions, immunological synapses, and neuronal synapses. In addition, it is involved in the cellular mechanisms of cell migration, cell process formation, cancer metastasis, and spermatogenesis. Lack of drebrin leads to the dysfunction of cell-cell communication, resulting in aberrant migration of metastatic cancer cells, aberrant synaptic function in dementia, and rupture of endothelial integrity. Because drebrin forms a unique F-actin with a longer helical crossover, drebrin may create an F-actin platform for molecular assembly and play a pivotal role in intercellular communication.