Gene Discovery: Identifying Protein Kinases Necessary for Synapse Development in the Mammalian CNS

The transfer of electrical or chemical signals between neurons via synapses not only allows cells to communicate with one another, it also mediates communication between the central nervous system and other regions of the body. The importance of cellular communication is emphasized when considering developmental diseases such as autism and mental retardation where breaks in communication are thought be involved in the disorders. Thus it is important to understand how synapses are formed and which molecules are involved in synapse development. Despite the prominence of protein kinases in the mammalian genome, little is known about which protein kinases specifically affect glutamatergic and GABAergic synapses. Here, we perform a novel RNAi-based loss-of-function forward genetic screen to identify kinases that mediate either excitatory or inhibitory synapse development in cultured hippocampal neurons from mice. So far, we identified several protein kinases that are important for proper synapse development.  One example is a MLTK-family kinase, which decreases excitatory synapse density when knocked down using siRNA. Future work will be conducted to elucidate the mechanism used by the MLTK-family kinase in synapse formation.