The GTP-binding protein Septin 7 is critical for dendrite branching and dendritic-spine morphology.
Septins, a highly conserved family of GTP-binding proteins, were originally identified in a genetic screen for S. cerevisiae mutants defective in cytokinesis [1, 2]. In yeast, septins maintain the compartmentalization of the yeast plasma membrane during cell division by forming rings at the cortex of the bud neck, and these rings establish a lateral diffusion barrier. In contrast, very little is known about the functions of septins in mammalian cells [3, 4] including postmitotic neurons [5-7]. Here, we show that Septin 7 (Sept7) localizes at the bases of filopodia and at branch points in developing hippocampal neurons. Upon downregulation of Sept7, dendritic branching is impaired. In mature neurons, Sept7 is found at the bases of dendritic spines where it associates with the plasma membrane. Mature Sept7-deficient neurons display elongated spines. Furthermore, Sept5 and Sept11 colocalize with and coimmunoprecipitate with Sept7, thereby arguing for the existence of a Septin5/7/11 complex. Taken together, our findings show an important role for Sept7 in regulating dendritic branching and dendritic-spine morphology. Our observations concur with data from yeast, in which downregulation of septins yields elongated buds, suggesting a conserved function for septins from yeast to mammals.
Xie
Yunli
Y
Department of Neural Cell Biology, Center for Brain Research, Medical University of Vienna, Vienna A1090, Austria.
Vessey
John P
JP
Konecna
Anetta
A
Dahm
Ralf
R
Macchi
Paolo
P
Kiebler
Michael A
MA
D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D046912:Multiprotein Complexes; D009154:Mutation; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D011554:Pseudopodia / Q000378:metabolism / Q000648:ultrastructure; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D058112:Septins; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; D020558:GTP Phosphohydrolases; C512894:Septin7 protein, rat; D058112:Septins