Growth of neurite processes from the cell body is the critical step in neuronal development and involves a large increase in cell membrane surface area¹. Arachidonic-acid-releasing phospholipases are highly enriched in nerve growth cones and have previously been implicated in neurite outgrowth^{2, 3}. Cell membrane expansion is achieved through the fusion of transport organelles with the plasma membrane⁴; 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.

1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK

Correspondence to: Bazbek Davletov¹ Correspondence and requests for materials should be addressed to B.D. (Email: email@bazbek.com).

Received 30 November 2005 | Accepted 21 December 2005

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