an obsl1-cul7fbxw8 ubiquitin ligase signaling mechanism regulates golgi morphology and dendrite patterning一个obsl1-cul7fbxw8泛素连接酶信号机制调节高尔基体形态和树突模式.pdfVIP

An OBSL1-Cul7Fbxw8 Ubiquitin Ligase Signaling Mechanism Regulates Golgi Morphology and Dendrite Patterning 1,2 1 1 1 1 Nadia Litterman , Yoshiho Ikeuchi , Gilbert Gallardo , Brenda C. O’Connell , Mathew E. Sowa , 3 1 1,2 Steven P. Gygi , J. Wade Harper , Azad Bonni * 1 Department of Pathology, Harvard Medical School, Boston, Massachusetts, United States of America, 2 Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, United States of America, 3 Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, United States of America Abstract The elaboration of dendrites in neurons requires secretory trafficking through the Golgi apparatus, but the mechanisms that govern Golgi function in neuronal morphogenesis in the brain have remained largely unexplored. Here, we report that the E3 ubiquitin ligase Cul7Fbxw8 localizes to the Golgi complex in mammalian brain neurons. Inhibition of Cul7Fbxw8 by independent approaches including Fbxw8 knockdown reveals that Cul7Fbxw8 is selectively required for the growth and elaboration of dendrites but not axons in primary neurons and in the developing rat cerebellum in vivo. Inhibition of Cul7Fbxw8 also dramatically impairs the morphology of the Golgi complex, leading to deficient secretory trafficking in neurons. Using an immunoprecipitation/mass spectrometry screening approach, we also uncover the cytoskeletal adaptor protein OBSL1 as a critical regulator of Cul7Fbxw8 in Golgi morphogenesis and dendrite elaboration. OBSL1 forms a physical complex with the