The brain is composed of a multitude of neurons - highly polarized cells that are found throughout the nervous system. Indeed, the human brain has more than 100 billion neurons. These neurons are connected with each other by cell-cell junctions called "synapses", which enable higher brain functions, such as learning and memory, thought, vision, consciousness, and so on. Therefore, elucidation of the molecular mechanisms of synapse development will ultimately lead to an understanding of not only neural circuit formation, but also of brain development, which would definitely contribute to an improved understanding of numerous human diseases, such as Alzheimer's, Parkinson's, and other neurological diseases (including schizophrenia); leading as well to other advances in the field of basic neuroscience.

The synapse possesses a unique structure composed of a presynaptic nerve terminal, synaptic cleft, and a postsynaptic structure (see Figure). In the last decade, a number of molecules that are localized at synapses have been isolated and characterized, but we are still far from a complete understanding of the molecular organization and function of synapses. Our laboratory has focused on the molecular mechanisms of the assembly of the presynaptic active zone, which as a specialized site for neurotransmitter release, is believed to play several crucial roles in synaptic vesicle cycling as well as in the formation of functional synapses. Recently, we identified a novel active zone-specific protein named CAST (Cytomatrix at the Active zone-associated STructural protein), which binds other active zone proteins like RIM, Bassoon, Piccolo, and Munc13 to form a large molecular complex at the active zone, indicating that CAST is a key molecule in the organization of the active zone, and thus in neurotransmitter release.

Our ultimate goal is to fully clarify the complex mechanisms of generation, maintenance, and disruption of synapses; mainly by focusing on the structure and function of the presynaptic active zone.

Takao-Rikitsu, E., Mochida, S., Inoue, E., Deguchi-Tawarada, M., Inoue, M., Ohtsuka, T.*, and Takai, Y. 2004. Physical and functional interaction of the active zone proteins, CAST, RIM1, and Bassoon, in neurotransmitter release. J. Cell Biol. 164:301-311. (*corresponding author)

Deguchi-Tawarada, M., Inoue, E., Takao-Rikitsu, E., Inoue, M., Ohtsuka, T.*, and Takai, Y. 2004. CAST2: identification and characterization of a protein structurally related to the presynaptic cytomatrix protein CAST. Genes Cells 9:15-23. (*corresponding author)

Ohtsuka, T.*, Takao-Rikitsu, E., Inoue, E., Inoue, M., Takeuchi, M., Matsubara, K., Deguchi-Tawarada, M., Satoh, K., Morimoto, K., Nakanishi, H., and Takai, Y*. 2002. CAST: a novel protein of the cytomatrix at the active zone of synapses that forms a ternary complex with RIM1 and Munc13-1. J. Cell Biol. 158: 577-590. (*corresponding author)