L1 sticks around

icrotubule (MT) assembly is a dynamic process involving the addition and removal of tubulin ␣␤ heterodimers. The binding of microtubule-associated proteins (MAPs) to MTs helps to prevent depolymerization M of assembled filaments. Despite years of study, there has been little consensus on the structural basis for this stabilization. Open a number of textbooks on the subject, and you are likely to find that some show MAP proteins wrapping around the microtubule, binding together the protofilaments, while others picture MAPs binding lengthwise along individual protofilaments. On page 1187, Al-Bassam et al. finally resolve the structural basis for MAP stabilization of microtubules MAP2 and tau (orange) bind along microtubule protofilaments (blue). by examining the MAP2/tau family. Stabilization of MTs by MAP2/tau proteins is required during axon and dendrite development. Although both MAP2 and the COOH terminus of tubulin with which it interacts are unstructured in solution, L1 sticks around he cell adhesion molecule (CAM) L1 is important for the growth of axons during neuronal development—mutations in L1 cause birth defects and neurological disorders. Although its extracellular domain mediates cell-to-cell adhesion, the cytoplasmic domain of L1 determines the stickiness of this CAM by regulating its rate of internalization, according to new results from Schaefer et al. on page 1223. The new report shows that phosphorylation of the cytoplasmic domain makes L1 more adhesive by preventing its endocytosis. The residue Tyr1176, which is specific to the neuronal isoform of L1, was phosphorylated in vitro by the nonreceptor tyrosine kinase p60src. In vivo, phosphorylation of L1 prevented its endocytosis by inhibiting its interaction with the clathrin-associated AP-2 complex. Homophilic binding to L1 on a neighboring cell caused its dephosphorylation, which should promote endocytosis. As predicted, unphosphorylated L1 was found at sites of cell contact and in cytoplasmic vesicles. A second article in this issue, by Dickson et al. (page 1105), demonstrates that this same AP-2–binding domain also interacts with the cytoskeletal protein ezrin. Disrupting L1 interaction with ezrin family members promoted axon branching, indicating that the interaction normally stabilizes engagement of the plasma membrane and the cytoskeleton. T It will be interesting to determine whether phosphorylation of L1 also influences its binding to ezrin, revealing a simple molecular switch for regulation of L1 interaction partners. In this scenario, L1 at the front of the growth cone is phosphorylated, possibly by a src family kinase. Interaction with L1 in a nearby cell results in binding to …