A Signaling Lipid Drives Synapse Formation

Brain function relies on the accurate formation of synaptic contacts, and alterations in this process are implicated in disease, including some psychiatric and neurodevelopmental disorders. Synapse formation requires the synthesis and transport of presynaptic proteins from the soma (which contains the nucleus) to the axon terminal. The identity and regulation of the transport organelle or organelles that are responsible for the assembly of presynaptic sites is not yet clear. On page 223 of this issue, Rizalar et al. ( 1 ) define the ultrastructure of these organelles and show that they are precursor vesicles that transport several types of presynaptic proteins at once. They also show that the signaling lipid phosphatidylinositol 3,5-bisphosphate [PI(3,5)P 2 ] plays a key role in their transport along the axon by binding to kinesin family member 1A (KIF1A), which is a microtubule-dependent motor protein. Further investigation may aid the development of therapies for disorders that are characterized by defective synapses.