Tau-441 (2N4R) P301S Mutant Monomers

Mammalian N-glycosylation is present on CHO-secreted tau 2N4R, which contributes to slower migration on SDS-PAGE than E.coli or Baculovirus/Sf9 expressed tau (1, 2) . N-glycosylated tau has been identified in human AD-diseased brains, but not healthy brains, and may precede tau hyperphosphorylation (3, 4) . N-glycosylation of Tau has been demonstrated to affect its aggregation propensity (5) . The tau P301S mutation is associated with early onset neurodegeneration, and functionally reduces microtubule assembly and stimulates fibril assembly (6, 7) . Our CHO-expressed Tau 2N4R P301S will readily form fibrils in the absence of heparin and contains mammalian post-translational modifications that may better mimic tau in human AD-brains.

GGSHHHHHHHHHHGSGGSENLYFQGMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVSGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL

CHO expression in mammalian cell line may lead to more “human” like phosphorylation/glycosylation patterns. For corresponding PFFs, see catalog# SPR-516.

1. Guo et al., 2019. A pathogenic tau fragment compromises microtubules, disrupts insulin signaling and induces the unfolded protein response. Acta Neuropathologica Communications. DOI: 10.1186/s40478-018-0651-9 2. Losev et al., 2020. Differential effects of putative N-glycosylation sites in human Tau on Alzheimer’s disease-related neurodegeneration. Cellular and Molecular Life Sciences. DOI: 10.1007/s00018-020-03643-3 3. Zhang et al., 2020. Integrative glycoproteomics reveals protein N-glycosylation aberrations and glycoproteomic network alterations in Alzheimer’s disease. Sci. Adv. DOI: 10.1126/sciadv.abc5802 4. Liu et al., 2002. Role of glycosylation in hyperphosphorylation of tau in Alzheimer’s disease. FEBS. DOI: 10.1016/S0014-5793(02)02228-7 5. Losev et al., 2019. Novel model of secreted human tau protein reveals the impact of the abnormal N-glycosylation of tau on its aggregation propensity. Sci. Rep. https://doi.org/10.1038/s41598-019-39218-x 6. Bugiani et al., 1999. Frontotemporal Dementia and Corticobasal Degeneration in a Family with a P301S Mutation in Tau. J Neuropathol Exp Neurol. doi: 10.1097/00005072-199906000-00011. 7. Goedert and Crowther, 1999. Effects of frontotemporal dementia FTDP-17 mutations on heparin-induced assembly of tau filaments. FEBS Lett. DOI: 10.1016/s0014-5793(99)00508-6

CHO expression in mammalian cell line may lead to more “human” like phosphorylation/glycosylation patterns. For corresponding PFFs, see catalog# SPR-516.

1. Guo et al., 2019. A pathogenic tau fragment compromises microtubules, disrupts insulin signaling and induces the unfolded protein response. Acta Neuropathologica Communications. DOI: 10.1186/s40478-018-0651-9 2. Losev et al., 2020. Differential effects of putative N-glycosylation sites in human Tau on Alzheimer’s disease-related neurodegeneration. Cellular and Molecular Life Sciences. DOI: 10.1007/s00018-020-03643-3 3. Zhang et al., 2020. Integrative glycoproteomics reveals protein N-glycosylation aberrations and glycoproteomic network alterations in Alzheimer’s disease. Sci. Adv. DOI: 10.1126/sciadv.abc5802 4. Liu et al., 2002. Role of glycosylation in hyperphosphorylation of tau in Alzheimer’s disease. FEBS. DOI: 10.1016/S0014-5793 (02) 02228-7 5. Losev et al., 2019. Novel model of secreted human tau protein reveals the impact of the abnormal N-glycosylation of tau on its aggregation propensity. Sci. Rep. https://doi.org/10.1038/s41598-019-39218-x 6. Bugiani et al., 1999. Frontotemporal Dementia and Corticobasal Degeneration in a Family with a P301S Mutation in Tau. J Neuropathol Exp Neurol. doi: 10.1097/00005072-199906000-00011. 7. Goedert and Crowther, 1999. Effects of frontotemporal dementia FTDP-17 mutations on heparin-induced assembly of tau filaments. FEBS Lett. DOI: 10.1016/s0014-5793 (99) 00508-6

GGSHHHHHHHHHHGSGGSENLYFQGMAEPRQEFEVMEDHAGTYGLGDRKDQGGYTMHQDQEGDTDAGLKESPLQTPTEDGSEEPGSETSDAKSTPTAEDVTAPLVDEGAPGKQAAAQPHTEIPEGTTAEEAGIGDTPSLEDEAAGHVTQARMVSKSKDGTGSDDKKAKGADGKTKIATPRGAAPPGQKGQANATRIPAKTPPAPKTPPSSGEPPKSGDRSGYSSPGSPGTPGSRSRTPSLPTPPTREPKKVAVVRTPPKSPSSAKSRLQTAPVPMPDLKNVKSKIGSTENLKHQPGGGKVQIINKKLDLSNVQSKCGSKDNIKHVSGGGSVQIVYKPVDLSKVTSKCGSLGNIHHKPGGGQVEVKSEKLDFKDRVQSKIGSLDNITHVPGGGNKKIETHKLTFRENAKAKTDHGAEIVYKSPVVSGDTSPRHLSNVSSTGSIDMVDSPQLATLADEVSASLAKQGL