title: Ndfip1 is required for the development of pyramidal neuron dendrites and spines in the neocortex.
abstract: Ubiquitin ligases of the Nedd4 family are important for axon and dendrite development, but little is known about their adaptor, Nedd4 family-interacting protein 1 (Ndfip1), that is responsible for their enzymatic activation. To study the function of Ndfip1 in cortical development, we generated a conditional knock-out (conditional KO) in neurons. The Ndfip1 conditional KO mice were viable; however, cortical neurons in the adult brain exhibited atrophic characteristics, including stunted dendritic arbors, blebbing of dendrites, and fewer dendritic spines. In electron micrographs, these neurons appeared shrunken with compacted somata and involutions of the nuclear membrane. In culture, Ndfip1 KO neurons exhibited exuberant sprouting suggesting loss of developmental control. Biochemical analysis of postsynaptic density (PSD) fractions from Ndfip1 KO cortical and hippocampal neurons showed that the postsynaptic proteins (Arc and PSD-95) were reduced compared with wild-type controls. In addition, the PI3 kinase/Akt signaling pathway was altered. These results indicate that Ndfip1, through its Nedd4 effectors, is important for the development of dendrites and dendritic spines in the cortex.
authors.affiliation: Florey Institute of Neuroscience and Mental Health and.
authors.forename: Vicki E
authors.initials: VE
authors.lastname: Hammond
authors.affiliation: Florey Institute of Neuroscience and Mental Health and Department of Anatomy and Neuroscience, The University of Melbourne, Victoria 3010, Australia.
authors.forename: Jenny M
authors.initials: JM
authors.lastname: Gunnersen
authors.affiliation: Florey Institute of Neuroscience and Mental Health and.
authors.forename: Choo-Peng
authors.initials: CP
authors.lastname: Goh
authors.affiliation: Florey Institute of Neuroscience and Mental Health and.
authors.forename: Ley-Hian
authors.initials: LH
authors.lastname: Low
authors.affiliation: Florey Institute of Neuroscience and Mental Health and.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hyakumura
authors.affiliation: Florey Institute of Neuroscience and Mental Health and.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Tang
authors.affiliation: Florey Institute of Neuroscience and Mental Health and.
authors.forename: Joanne M
authors.initials: JM
authors.lastname: Britto
authors.affiliation: Florey Institute of Neuroscience and Mental Health and.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Putz
authors.affiliation: Florey Institute of Neuroscience and Mental Health and.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Howitt
authors.affiliation: Florey Institute of Neuroscience and Mental Health and.
authors.forename: Seong-Seng
authors.initials: SS
authors.lastname: Tan
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000235:genetics*; D002458:Cell Fractionation; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019579:Neocortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017966:Pyramidal Cells / Q000000981:diagnostic imaging*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014463:Ultrasonography; D000099260:Empty Spiracles Homeobox Proteins
chemical_list: D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D064231:Nestin; D051059:PTEN Phosphohydrolase; D051057:Proto-Oncogene Proteins c-akt; D014157:Transcription Factors; D000099260:Empty Spiracles Homeobox Proteins; C501447:Dlg4 protein, mouse; C499188:Ndfip1 protein, mouse; C485184:enhanced green fluorescent protein
keywords: Nedd4; dendrites; development; spines; ubiquitin ligase