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Role of Septin Cytoskeleton in Spine Morphogenesis and Dendrite Development in Neurons

2007; Elsevier BV; Volume: 17; Issue: 20 Linguagem: Inglês

10.1016/j.cub.2007.09.039

1879-0445

Tomoko Tada, Alyson Simonetta, Matthew N. Batterton, Makoto Kinoshita, Dieter Edbauer, Morgan Sheng,

Fermentation and Sensory Analysis

Septins are GTP-binding proteins that polymerize into heteromeric filaments and form microscopic bundles or ring structures in vitro and in vivo. Because of these properties and their ability to associate with membrane, F-actin, and microtubules, septins have been generally regarded as cytoskeletal components [1Kinoshita M. Field C.M. Coughlin M.L. Straight A.F. Mitchison T.J. Self- and actin-templated assembly of Mammalian septins.Dev. Cell. 2002; 3: 791-802Abstract Full Text Full Text PDF PubMed Scopus (379) Google Scholar, 2Kinoshita M. Diversity of septin scaffolds.Curr. Opin. Cell Biol. 2006; 18: 54-60Crossref PubMed Scopus (138) Google Scholar]. Septins are known to play roles in cytokinesis, in membrane trafficking, and as structural scaffolds; however, their function in neurons is poorly understood. Many members of the septin family, including Septin 7 (Sept7), were found by mass-spectrometry analysis of postsynaptic density (PSD) fractions of the brain [3Peng J. Kim M.J. Cheng D. Duong D.M. Gygi S.P. Sheng M. Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry.J. Biol. Chem. 2004; 279: 21003-21011Crossref PubMed Scopus (371) Google Scholar, 4Collins M.O. Husi H. Yu L. Brandon J.M. Anderson C.N. Blackstock W.P. Choudhary J.S. Grant S.G. Molecular characterization and comparison of the components and multiprotein complexes in the postsynaptic proteome.J. Neurochem. 2005; 1: 16-23Google Scholar], suggesting a possible postsynaptic function of septins in neurons. We report that Sept7 is localized at the base of dendritic protrusions and at dendritic branch points in cultured hippocampal neurons—a distribution reminiscent of septin localization in the bud neck of budding yeast. Overexpression of Sept7 increased dendrite branching and the density of dendritic protrusions, whereas RNA interference (RNAi)-mediated knockdown of Sept7 led to reduced dendrite arborization and a greater proportion of immature protrusions. These data suggest that Sept7 is critical for spine morphogenesis and dendrite development during neuronal maturation.