The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis

Spine function requires precise control of the actin cytoskeleton. Kalirin- 7, a GDP/GTP exchange factor for Rad, interacts with PDZ proteins such as P SD-95, colocalizing with PSD-95 at synapses of cultured hippocampal neurons . PSD-95 and Kalirin-7 interact in vivo and in heterologous expression syst ems. In primary cortical neurons, transfected Kalirin-7 is targeted to spin es and increases the number and size of spine-like structures. A Kalirin-7 mutant unable to interact with PDZ proteins remains in the cell soma, induc ing local formation of aberrant filopodial neurites. Kalirin-7 with an inac tivated GEF domain reduces the number of spines below control levels. These results provide evidence that PDZ proteins target Kalirin-7 to the PSD, wh ere it regulates dendritic morphogenesis through Rad signaling to the actin cytoskeleton.