Journal article
Loss of tau and Fyn reduces compensatory effects of MAP2 for tau and reveals a Fyn-independent effect of tau on calcium
Journal of neuroscience research, Vol.97(11), pp.1393-1413
11/2019
DOI: 10.1002/jnr.24517
PMCID: PMC6850396
PMID: 31452242
Abstract
Microtubule-associated protein tau associates with Src family tyrosine kinase Fyn and is tyrosine phosphorylated by Fyn. The presence of tyrosine phosphorylated tau in AD and the involvement of Fyn in AD has drawn attention to the tau-Fyn complex. In this study, a tau-Fyn double knockout (DKO) mouse was generated to investigate the role of the complex. DKO mice resembled Fyn KO in novel object recognition and contextual fear conditioning tasks and resembled tau KO mice in the pole test and protection from pentylenetetrazole-induced seizures. In glutamate-induced Ca
2+
response, Fyn KO was decreased relative to WT and DKO had a greater reduction relative to Fyn KO, suggesting that tau may have a Fyn-independent role. Since tau KO resembled WT in its Ca
2+
response, we investigated whether MAP2 served to compensate for tau, since the MAP2 level was increased in tau KO but decreased in DKO mice. We found that like tau, MAP2 increased Fyn activity. Moreover, tau KO neurons had increased density of dendritic MAP2-Fyn complexes relative to WT neurons. Therefore, we hypothesize that in the tau KO, the absence of tau would be compensated by MAP2, especially in the dendrites, where tau-Fyn complexes are of critical importance. In the DKO, decreased levels of MAP2 made compensation more difficult, thus revealing the effect of tau in the Ca
2+
response.
Details
- Title: Subtitle
- Loss of tau and Fyn reduces compensatory effects of MAP2 for tau and reveals a Fyn-independent effect of tau on calcium
- Creators
- Guanghao Liu - Interdisciplinary Program in Neuroscience, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USARamasamy Thangavel - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAJacob Rysted - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAYohan Kim - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAMeghan B Francis - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAEric Adams - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAZhihong Lin - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USARebecca J Taugher - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAJohn A Wemmie - Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAYuriy M Usachev - Department of Pharmacology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAGloria Lee - Department of Internal Medicine, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Journal of neuroscience research, Vol.97(11), pp.1393-1413
- DOI
- 10.1002/jnr.24517
- PMID
- 31452242
- PMCID
- PMC6850396
- NLM abbreviation
- J Neurosci Res
- ISSN
- 0360-4012
- eISSN
- 1097-4547
- Grant note
- DOI: 10.13039/100000957, name: Alzheimer's Association, award: IIRG‐12‐241042; DOI: 10.13039/100000065, name: National Institute of Neurological Disorders and Stroke, award: R01 NS096246; DOI: 10.13039/100000049, name: National Institute on Aging, award: F30 AG054134, R01 AG017753
- Language
- English
- Date published
- 11/2019
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Psychiatry; Iowa Neuroscience Institute; Anesthesia; Neuroscience and Pharmacology; Immunology; Neurosurgery; Internal Medicine
- Record Identifier
- 9984066139902771
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