The lipid phosphatase PTEN - a tumour suppressor - antagonises PI 3-kinase (PI3K) to control cellular levels of 3′-phosphorylated phosphoinositides. Together PTEN and PI3K control cell cycle progression, cytoskeletal rearrangements and cell polarisation in a variety of systems. On , Britta Eickholt and co-workers add axonal extension in neurons to the list. Semaphorin 3A is an inhibitory guidance cue that can induce collapse of the extending neuronal growth cone by activating the kinase GSK3. Eickholt and co-workers now demonstrate that PTEN is essential for this effect, since they can block it with a dominant-negative PTEN mutant and peptides that activate PI3K. In addition, they use live imaging of a GFP-PTEN construct to show that semaphorin 3A causes PTEN to move from microtubules in the central region of the growth cone to the growth cone membrane. The sequestration of PTEN on microtubules in the growth cone is reminiscent of the spatial restriction of PTEN and PI3K that generates internal phospholipid gradients to drive cell polarisation and chemotaxis in Dictyostelium. A similar mechanism may therefore operate in neuronal growth cones.
