1. Ndfip1 Is Required for the Development of Pyramidal Neuron Dendrites and Spines in the Neocortex
- Author
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Jenny M. Gunnersen, Ulrich Putz, Joanne M. Britto, Michelle M. Tang, Seong-Seng Tan, Vicki E. Hammond, Choo-Peng Goh, Ley-Hian Low, Jason Howitt, and Tomoko Hyakumura
- Subjects
Dendritic spine ,Dendritic Spines ,Cognitive Neuroscience ,Green Fluorescent Proteins ,Mice, Transgenic ,Neocortex ,Dendrite ,Biology ,Cell Fractionation ,Transfection ,Nestin ,Mice ,Cellular and Molecular Neuroscience ,Postsynaptic potential ,medicine ,Animals ,Axon ,Cells, Cultured ,Ultrasonography ,Homeodomain Proteins ,Dendritic spike ,Pyramidal Cells ,PTEN Phosphohydrolase ,Gene Expression Regulation, Developmental ,Membrane Proteins ,Embryo, Mammalian ,Dendritic filopodia ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Animals, Newborn ,nervous system ,Intercellular Signaling Peptides and Proteins ,Carrier Proteins ,Disks Large Homolog 4 Protein ,Guanylate Kinases ,Proto-Oncogene Proteins c-akt ,Neuroscience ,Postsynaptic density ,Transcription Factors - 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.
- Published
- 2013
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