Tubulin and the postsynaptic density: A tubulin-based structure model

The presence and roles of tubulin in and around the postsynaptic density have long been debated, despite reports of tubulin immunoreactivity in the postsynaptic density as early as 1975. This question remains unresolved, and the significance of tubulin in the postsynaptic density remains insufficiently understood. Recently, my research group developed a novel purification protocol for the postsynaptic density lattice and used it to investigate the structure and functions of the postsynaptic density. This review summarizes and discusses recent findings from studies by my team, in which my team demonstrated that tubulin is a key molecule in postsynaptic density organization and function. Since 2018, we have published three papers addressing this theme, culminating in the proposal of a new model of postsynaptic density molecular organization that highlights a fundamental role for tubulin at excitatory synapses. In particular, this review outlines the conceptual development of a tubulin-based model of postsynaptic density architecture derived from analyses of purified postsynaptic density lattice. The initial model integrated scaffold/adaptor protein assembly with the postsynaptic density lattice structural framework. This was refined into the "postsynaptic density lattice platform model," in which non-microtubule tubulin-based postsynaptic density lattice structures provide platforms for the recruitment and organization of postsynaptic density scaffold/adaptor proteins and other postsynaptic density-associated molecules during synapse maturation and remodeling. This updated concept underscores the potential importance of tubulin in the postsynaptic density. Additionally, the review traces nearly 50 years of research on postsynaptic density tubulin and evaluates its significance from multiple perspectives, together with recent findings by my team. Our results suggest that tubulin plays a central role in the formation and function of both the postsynaptic density and postsynaptic density lattice. Future research focusing on structures formed by non-microtubule tubulin is expected to provide new insights. Unlike the well-recognized role of actin in dendritic spines, the importance of tubulin in the postsynaptic density is not yet widely appreciated. I emphasize the need for further multifaceted investigations to uncover novel tubulin-based mechanisms underlying postsynaptic density structure and function.