Article: Tau interacts with SHP2 in neuronal systems and in Alzheimer’s disease
Authors: Yohan Kim, Guanghao Liu, Chad J. Leugers, Joseph D. Mueller, Meghan B. Francis, Marco M. Hefti, Julie A. Schneider, Gloria Lee
Journal: J Cell Sci. 2019 Jun 14. pii: jcs.229054. doi: 10.1242/jcs.229054. [Epub ahead of print]
Microtubule-associated protein tau, an integral component of neurofibrillary tangles, interacts with a variety of signaling molecules. Previously, our laboratory reported that NGF-induced MAPK activation in a PC12-derived cell line was potentiated by tau, with phosphorylation at T231 being required. Therefore, we sought to identify a signaling molecule involved in the NGF Ras-MAPK pathway that interacted with phospho-T231-tau. Here, we report that the protein tyrosine phosphatase SHP2 interacted with tau, with phospho-T231 significantly enhancing the interaction. Using proximity ligation assays, endogenous tau-SHP2 complexes were found in neuronal cells, where the number of tau-SHP2 complexes significantly increased when the cells were treated with NGF, with phosphorylation at T231 being required for the increase. The interaction did not require microtubule association and an association with activated SHP2 was also found. Tau-SHP2 complexes were found in both primary mouse hippocampal culture and adult mouse brain. Lastly, upregulated SHP2 was found in mild and severe AD patients and tau-SHP2 complexes were increased in Alzheimer’s disease patient samples. These findings strongly suggest a role for the tau-SHP2 interaction in NGF-stimulated neuronal development and in Alzheimer’s disease.
Link to journal online: https://jcs.biologists.org/content/early/2019/06/14/jcs.229054.long