Chen et al. identify a protein that links actin filaments to the plasma membrane in developing neurons, enabling the cells to send out new branches.

As the brain develops, neurons sprout extensions called filopodia that mature into dendrites, dendritic spines, and axons that allow the cells to communicate with other neurons. Elongation of a filopodium requires changes to the plasma membrane and to the actin cytoskeleton. For example, actin filaments polymerize and bunch up, forming bundles. Researchers aren't sure how the cell coordinates the membrane and actin renovations.

The surprising answer, Chen et al. suggest, is that a kinase does the job. The researchers discovered that the kinase GRK5 promotes filopodia formation, dendrite branching, and spine maturation. The C terminus of the protein latches onto actin filaments and spurs them to form bundles. The N terminus of GRK5 connects to the membrane phospholipid PI(4,5)P2. Preventing this interaction cuts the number of filopodia a cell can produce, Chen et al. showed. The researchers also determined that GRK5 is crucial for neural growth in vivo. Mice lacking the protein perform poorly on memory and learning tests, suggesting that their neurons aren't linking up properly.

Chen et al. hypothesize that GRK5 transmits changes in actin structure to an area of the membrane rich in PI(4,5)P2, which bulges in response, initiating a filopodium. However, GRK5 can perform its task even if it lacks its kinase activity, suggesting it is serving as a bridge between actin and the plasma membrane rather than triggering its effects enzymatically.

et al
J. Cell Biol.