Targeted disruption of Sept3, a heteromeric assembly partner of Sept5 and Sept7 in axons, has no effect on developing CNS neurons.
The septins constitute a family of GTPase proteins that are involved in many cytological processes such as cytokinesis and exocytosis. Previous studies have indicated that mammalian Sept3 is a brain-specific protein that is abundant in synaptic terminals. Here, we further investigated the localization and function of Sept3 in the mouse brain. Sept3 is expressed in several types of post-mitotic neurons, including granule cells in the cerebellum and pyramidal neurons in the cerebral cortex and hippocampus. In primary cultures of hippocampal pyramidal neurons, Sept3 protein is enriched at the tips of growing neurites during differentiation. Sept3 directly binds to Sept5 and Sept7 and forms a heteromeric complex at nerve terminals adjacent to where a synaptic vesicle marker, synaptophysin, is expressed in mature neurons. When over-expressed in HEK293 cells, Sept3 forms filamentous structures that are dependent on the presence of its GTP- and phosphoinositide-binding domains. To investigate the physiological roles of Sept3, we generated Sept3 deficient mice. These mice show no apparent abnormalities in histogenesis nor neuronal differentiation in culture. Expression of synaptic proteins and other septins are unaltered, indicating that Sept3 is dispensable for normal neuronal development.
Fujishima
Kazuto
K
Laboratory for Neural Cell Polarity, RIKEN Brain Science Institute, Saitama, Japan.
Kiyonari
Hiroshi
H
Kurisu
Junko
J
Hirano
Tomoo
T
Kengaku
Mineko
M
D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology*; D016367:Baculoviridae / Q000235:genetics; D018797:Cell Cycle Proteins / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D010716:Phosphatidylinositols / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000378:metabolism; D058112:Septins
D000199:Actins; D018797:Cell Cycle Proteins; D010716:Phosphatidylinositols; D011994:Recombinant Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C491612:Sept5 protein, mouse; C512895:Sept7 protein, mouse; D058112:Septins; C407343:septin 3; D005978:Glutathione