The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses
Open accessAbstract
The synapse is the primary locus of cell-cell communication in the nervous system. It is now clear that the synapse incorporates diverse cell signaling modalities in addition to classical neurotransmission. Here we show that two components of the insulin pathway are localized at CNS synapses, where they are components of the postsynaptic density (PSD). An immunochemical screen revealed that polypeptides of 58 and 53 kDa (p58/53) were highly enriched in PSD fractions from rat cerebral cortex, hippocampus, and cerebellum. These polypeptides were purified and microsequenced, revealing that p58/53 is identical to the insulin receptor tyrosine kinase substrate p58/53 (IRSp53). Our analysis of IRSp58/53 mRNA suggests that within rat brain there is one coding region for IRSp58 and IRSp53; we find no evidence of alternative splicing. We demonstrate that IRSp58/53 is expressed in the synapse-rich molecular layer of the cerebellum and is highly concentrated at the synapses of cultured hippocampal neurons, where it co-localizes with the insulin receptor. Together, these data suggest that insulin signaling may play a role at CNS synapses.
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Insulin receptors are present in the brain, where they are abundantly distributed in synaptic membranes of the cerebral cortex and hippocampus.
“IRs are present in the brain, where they are abundantly distributed in synaptic membranes of the cerebral cortex and hippocampus (Abbott et al., 1999; Havrankova et al., 1981; Marks et al., 1990; Unger and Betz, 1998).”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Abbott et al., 1999
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- Authors
- Abbott, M.-A., Wells, D. G., & Fallon, J. R.
- Affiliations
- University of Massachusetts Chan Medical School (US)
- Brown University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1999-09-01
- Volume
- 19
- Issue
- 17
- Pages
- 7300-7308
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6782521
- OpenAlex
- W1819107323
- Cited by
- 327
- References
- 45
- Citations by year
- 2026: 5 · 2025: 2 · 2024: 9 · 2023: 13 · 2022: 21 · 2021: 17 · 2020: 12 · 2019: 11 · 2018: 11 · 2017: 8 · 2016: 12 · 2015: 14 · 2014: 21 · 2013: 18 · 2012: 13
- FWCI
- 3.62
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship@UMassChan (submittedVersion)
- Funders
- American Heart Association
- Muscular Dystrophy Association
- National Institutes of Health (5r01mh053571-04)
- National Institute of Mental Health (MH53571)
- National Institute of Neurological Disorders and Stroke (F32NS010343, NS10343)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 23924, R01HD023924)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- IRSp53, insulin receptor, postsynaptic density, insulin signaling, cerebellum, hippocampal neurons, alternative splicing
- MeSH terms
- Amino Acid Sequence, Animals, Brain, Brain Chemistry, Cells, Cultured, Cerebellum, Hippocampus, Molecular Sequence Data, Nerve Tissue Proteins, Neurons, Phosphoproteins, Receptor, Insulin, Synapses, Synaptosomes, Electrophoresis, Gel, Two-Dimensional, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Reverse Transcriptase Polymerase Chain Reaction, Rats, Insulin Receptor Substrate Proteins
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