Omega-3 and omega-6 fatty acids stimulate cell membrane expansion by acting on syntaxin 3

Growth of neurite processes from the cell body is the critical step in neuronal development and involves a large increase in cell membrane surface area. Arachidonic-acid-releasing phospholipases are highly enriched in nerve growth cones and have previously been implicated in neurite outgrowth. Cell membrane expansion is achieved through the fusion of transport organelles with the plasma membrane; however, the identity of the molecular target of arachidonic acid has remained elusive. Here we show that syntaxin 3 (STX3), a plasma membrane protein, has an important role in the growth of neurites, and also serves as a direct target for omega-6 arachidonic acid. By using syntaxin 3 in a screening assay, we determined that the dietary omega-3 linolenic and docosahexaenoic acids can efficiently substitute for arachidonic acid in activating syntaxin 3. Our findings provide a molecular basis for the previously established action of omega-3 and omega-6 polyunsaturated fatty acids in membrane expansion at the growth cones, and represent the first identification of a single effector molecule for these essential nutrients.