An OBSL1-Cul7\(^{\text{Fbxw8}}\) Ubiquitin Ligase Signaling Mechanism Regulates Golgi Morphology and Dendrite Patterning

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An OBSL1-Cul7\(^{\text{Fbxw8}}\) Ubiquitin Ligase Signaling Mechanism Regulates Golgi Morphology and Dendrite Patterning

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dc.contributor.author Litterman, Nadia Kathryn
dc.contributor.author Ikeuchi, Yoshiho
dc.contributor.author Gallardo, Gilbert
dc.contributor.author O'Connell, Brenda C.
dc.contributor.author Sowa, Mathew E.
dc.contributor.author Gygi, Steven P.
dc.contributor.author Harper, J. Wade
dc.contributor.author Bonni, Azad
dc.date.accessioned 2012-01-20T21:35:27Z
dc.date.issued 2011
dc.identifier.citation Litterman, Nadia, Yoshiho Ikeuchi, Gilbert Gallardo, Brenda C. O'Connell, Mathew E. Sowa, Steven P. Gygi, J. Wade Harper, and Azad Bonni. 2011. An OBSL1-Cul7\(^{\text{Fbxw8}}\) ubiquitin ligase signaling mechanism regulates Golgi morphology and dendrite patterning. PLoS Biology 9(5): e1001060. en_US
dc.identifier.issn 1544-9173 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:7989737
dc.description.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 Cul7\(^{\text{Fbxw8}}\) localizes to the Golgi complex in mammalian brain neurons. Inhibition of Cul7\(^{\text{Fbxw8}}\) by independent approaches including Fbxw8 knockdown reveals that Cul7\(^{\text{Fbxw8}}\) 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 Cul7\(^{\text{Fbxw8}}\) 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 Cul7\(^{\text{Fbxw8}}\) in Golgi morphogenesis and dendrite elaboration. OBSL1 forms a physical complex with the scaffold protein Cul7 and thereby localizes Cul7 at the Golgi apparatus. Accordingly, OBSL1 is required for the morphogenesis of the Golgi apparatus and the elaboration of dendrites. Finally, we identify the Golgi protein Grasp65 as a novel and physiologically relevant substrate of Cul7\(^{\text{Fbxw8}}\) in the control of Golgi and dendrite morphogenesis in neurons. Collectively, these findings define a novel OBSL1-regulated Cul7\(^{\text{Fbxw8}}\) ubiquitin signaling mechanism that orchestrates the morphogenesis of the Golgi apparatus and patterning of dendrites, with fundamental implications for our understanding of brain development. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi://10.1371/journal.pbio.1001060 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3091842/pdf/ en_US
dash.license LAA
dc.subject biology en_US
dc.subject molecular cell biology en_US
dc.subject neuroscience en_US
dc.title An OBSL1-Cul7\(^{\text{Fbxw8}}\) Ubiquitin Ligase Signaling Mechanism Regulates Golgi Morphology and Dendrite Patterning en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS Biology en_US
dash.depositing.author Bonni, Azad
dc.date.available 2012-01-20T21:35:27Z
dash.affiliation.other HMS^Cell Biology en_US

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