Neuronal expression and interaction with the synaptic protein CASK suggest a role for Neph1 and Neph2 in synaptogenesis
- 27 July 2006
- journal article
- research article
- Published by Wiley in Journal of Comparative Neurology
- Vol. 498 (4), 466-475
- https://doi.org/10.1002/cne.21064
Abstract
Formation, differentiation, and plasticity of synapses require interactions between pre‐ and postsynaptic partners. Recently, it was shown that the transmembrane immunoglobulin superfamily protein SYG‐1 is required for providing synaptic specificity in C. elegans. However, it is unclear whether the mammalian orthologs of SYG‐1 are also involved in local cell interactions to determine specificity during synapse formation. We used in situ hybridization, immunohistochemistry, and immunogold electron microscopy to study the temporal and spatial expression of Neph1 and Neph2 in the developing and adult mouse brain. Both proteins show similar patterns with neuronal expression starting around embryonic days 12 and 11, respectively. Expression is strongest in areas of high migratory activity. In the adult brain, Neph1 and Neph2 are predominantly seen in the olfactory nerve layer and the glomerular layer of the olfactory bulb, in the hippocampus, and in Purkinje cells of the cerebellum. At the ultrastructural level, Neph1 and Neph2 are detectable within the dendritic shafts of pyramidal neurons. To a lesser extent, there is also synaptic localization of Neph1 within the stratum pyramidale of the hippocampal CA1 and CA3 region on both pre‐ and postsynaptic sites. Here it colocalizes with the synaptic scaffolder calmodulin‐associated serin/threonin kinase (CASK), and both Neph1 and Neph2 interact with the PDZ domain of CASK via their cytoplasmic tail. Our results show that Neph proteins are expressed in the developing nervous system of mammals and suggest that these proteins may have a conserved function in synapse formation or neurogenesis. J. Comp. Neurol. 498:466–475, 2006.Keywords
This publication has 28 references indexed in Scilit:
- Fasciclin II Signals New Synapse Formation through Amyloid Precursor Protein and the Scaffolding Protein dX11/MintJournal of Neuroscience, 2005
- NEPH2 Is Located at the Glomerular Slit Diaphragm, Interacts with Nephrin and Is Cleaved from Podocytes by MetalloproteinasesJournal of the American Society of Nephrology, 2005
- Signaling at the Slit DiaphragmJournal of the American Society of Nephrology, 2004
- Nephrin Expression Is Reduced in Human Diabetic NephropathyDiabetes, 2003
- Homodimerization and Heterodimerization of the Glomerular Podocyte Proteins Nephrin and NEPH1Journal of the American Society of Nephrology, 2003
- Shedding of plasma membrane proteinsCurrent topics in developmental biology, 2003
- Robo1 and Robo2 Are Homophilic Binding Molecules That Promote Axonal GrowthMolecular and Cellular Neuroscience, 2002
- Making Connections in the Fly Visual SystemNeuron, 2002
- Proteinuria and Perinatal Lethality in Mice Lacking NEPH1, a Novel Protein with Homology to NEPHRINMolecular and Cellular Biology, 2001
- CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexinsJournal of Neuroscience, 1996