Journal article
NMDA receptor-dependent regulation of dendritic spine morphology by SAP102 splice variants
The Journal of neuroscience, v 31(1), pp 89-96
05 Jan 2011
PMCID: PMC3030119
PMID: 21209193
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Membrane-associated guanylate kinases (MAGUKs) are major components of the postsynaptic density and play important roles in synaptic organization and plasticity. Most excitatory synapses are located on dendritic spines, which are dynamic structures that undergo morphological changes during synapse formation and plasticity. Synapse-associated protein 102 (SAP102) is a MAGUK that is highly expressed early in development and mediates receptor trafficking during synaptogenesis. Mutations in human SAP102 cause mental retardation, which is often accompanied with abnormalities in dendritic spines. However, little is known about the role of SAP102 in regulating synapse formation or spine morphology. We now find that SAP102 contains a novel NMDA receptor binding site in the N-terminal domain, which is specific for the NR2B subunit. The interaction between SAP102 and NR2B is PDZ (postsynaptic density-95/Discs large/zona occludens-1) domain independent and is regulated by alternative splicing of SAP102. We show that SAP102 that possesses an N-terminal insert is developmentally regulated at both mRNA and protein levels. In addition, expression of SAP102 increases synapse formation. Furthermore, the alternative splicing of SAP102 regulates dendritic spine morphology. SAP102 containing the N-terminal insert promotes lengthening of dendritic spines and preferentially promotes the formation of synapses at long spines, whereas a short hairpin RNA knockdown of the same SAP102 splice variant causes spine shrinkage. Finally, blocking NMDA receptor activity prevents the spine lengthening induced by the N-terminal splice variant of SAP102. Thus, our data provide the first evidence that SAP102 links NMDA receptor activation to alterations in spine morphology.
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Details
- Title
- NMDA receptor-dependent regulation of dendritic spine morphology by SAP102 splice variants
- Creators
- Bo-Shiun Chen - National Institute of Neurological Disorders and StrokeEleanor V Thomas - National Institutes of HealthAntonio Sanz-Clemente - National Institutes of HealthKatherine W Roche - National Institutes of Health
- Publication Details
- The Journal of neuroscience, v 31(1), pp 89-96
- Publisher
- Society for Neuroscience
- Grant note
- K99 NS057266-01 / NINDS NIH HHS Intramural NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000285915100011
- Scopus ID
- 2-s2.0-78650855101
- Other Identifier
- 991020099572504721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences