the 14-3-3ζ protein binds to the cell adhesion molecule l1, promotes l1 phosphorylation by ckii and influences l1-dependent neurite outgrowth14-3-3ζ蛋白结合的细胞粘附分子l1,促进l1磷酸化ckii和影响l1-dependent神经突的产物.pdf

The 14-3-3f Protein Binds to the Cell Adhesion Molecule L1, Promotes L1 Phosphorylation by CKII and Influences L1-Dependent Neurite Outgrowth 1 1 1,2 1,2 1,3 Elisa M. Ramser , Gerrit Wolters , Galina Dityateva , Alexander Dityatev , Melitta Schachner *, Thomas Tilling1 ¨ 1 Zentrum fur Molekulare Neurobiologie Hamburg, University of Hamburg, Hamburg, Germany, 2 Department of Neuroscience and Brain Technologies, Italian Institute of Technology, Genova, Italy, 3 Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey, United States of America Abstract Background: The cell adhesion molecule L1 is crucial for mammalian nervous system development. L1 acts as a mediator of signaling events through its intracellular domain, which comprises a putative binding site for 14-3-3 proteins. These regulators of diverse cellular processes are abundant in the brain and preferentially expressed by neurons. In this study, we investigated whether L1 interacts with 14-3-3 proteins, how this interaction is mediated, and whether 14-3-3 proteins influence the function of L1. Methodology/Principal Findings: By immunoprecipitation, we demonstrated that 14-3-3 proteins are associated with L1 in mouse brain. The site of 14-3-3 interaction in the L1 intracellular domain (L1ICD), which was identified by site-directed mutagenesis and direct binding assays, is phosphorylated by casein kinase II (CKII), and CKII phosphorylation of the L1ICD enhances binding of the 14-3-3 zeta isoform (14-3-3f). Interestingly, in an in vitro phosphorylation assay, 14-3-3f promoted CKII-dependent phosphorylati