[Synaptic development and abnormality at protein level]

A pyramidal neuron in the adult brain has numerous dendritic spines, which are typical postsynaptic structures. The shapes of spines are abnormal in the case of mental retardation, epilepsy, or Fragile X syndrome. Since the spine is thought to be a fundamental element in synaptic function, the abnormal shape of the spine is thought to be directly associated with brain dysfunction in the above diseases. Spine shape is regulated by each cytoskeletal protein. Over-expression of drebrin, a major actin-binding protein in the spine, elongates the spine. In the brain of Alzheimer's disease and Down syndrome, drebrin is greatly reduced. This indicates the structural abnormality of the spine as pathogenesis in the dementia. Now the spine morphogenesis comes into the spotlight. Although spines are thought to be formed from dendritic filopodia, the conversion mechanism of filopodia to spines has not been fully elucidated. We have recently demonstrated that cluster formation of drebrin-actin complex in filopodia is a key step for this conversion. When the cluster formation is inhibited, PSD-95 is not accumulated at postsynaptic sites. Since the drebrin-A isoform is necessary for the cluster formation, the regulation of drebrin A expression is now a focus in the field of spine formation.