Microtubule-associated protein tau is essential for long-term depression in the hippocampus

Tetsuya Kimura; Daniel Whitcomb; Jihoon Jo; Philip Regan; Thomas Piers; Seonghoo Heo; Christopher Martin Brown; Tsutomu Hashikawa; Miyuki Murayama; Heon Seok; Ioannis Sotiropoulos; Eunjoon Kim; Graham Collingridge; Akihiko Takashima; Kwangwook Cho

doi:10.1098/rstb.2013.0144

Microtubule-associated protein tau is essential for long-term depression in the hippocampus

Tetsuya Kimura, Daniel Whitcomb, Jihoon Jo, Philip Regan, Thomas Piers, Seonghoo Heo, Christopher Martin Brown, Tsutomu Hashikawa, Miyuki Murayama, Heon Seok, Ioannis Sotiropoulos, Eunjoon Kim, Graham Collingridge, Akihiko Takashima, Kwangwook Cho

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Abstract

The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.

Original language	English
Number of pages	8
Journal	Philosophical Transactions of the Royal Society B
Volume	369
Issue number	1633
DOIs	https://doi.org/10.1098/rstb.2013.0144
Publication status	Published - 5 Jan 2014

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20130144.fullFinal published version, 915 KBLicence: CC BY

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Kimura, T., Whitcomb, D., Jo, J., Regan, P., Piers, T., Heo, S., Brown, C. M., Hashikawa, T., Murayama, M., Seok, H., Sotiropoulos, I., Kim, E., Collingridge, G., Takashima, A., & Cho, K. (2014). Microtubule-associated protein tau is essential for long-term depression in the hippocampus. Philosophical Transactions of the Royal Society B, 369(1633). https://doi.org/10.1098/rstb.2013.0144

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title = "Microtubule-associated protein tau is essential for long-term depression in the hippocampus",

abstract = "The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.",

author = "Tetsuya Kimura and Daniel Whitcomb and Jihoon Jo and Philip Regan and Thomas Piers and Seonghoo Heo and Brown, {Christopher Martin} and Tsutomu Hashikawa and Miyuki Murayama and Heon Seok and Ioannis Sotiropoulos and Eunjoon Kim and Graham Collingridge and Akihiko Takashima and Kwangwook Cho",

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doi = "10.1098/rstb.2013.0144",

language = "English",

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Kimura, T, Whitcomb, D, Jo, J, Regan, P, Piers, T, Heo, S, Brown, CM, Hashikawa, T, Murayama, M, Seok, H, Sotiropoulos, I, Kim, E, Collingridge, G, Takashima, A & Cho, K 2014, 'Microtubule-associated protein tau is essential for long-term depression in the hippocampus', Philosophical Transactions of the Royal Society B, vol. 369, no. 1633. https://doi.org/10.1098/rstb.2013.0144

TY - JOUR

T1 - Microtubule-associated protein tau is essential for long-term depression in the hippocampus

AU - Kimura, Tetsuya

AU - Whitcomb, Daniel

AU - Jo, Jihoon

AU - Regan, Philip

AU - Piers, Thomas

AU - Heo, Seonghoo

AU - Brown, Christopher Martin

AU - Hashikawa, Tsutomu

AU - Murayama, Miyuki

AU - Seok, Heon

AU - Sotiropoulos, Ioannis

AU - Kim, Eunjoon

AU - Collingridge, Graham

AU - Takashima, Akihiko

AU - Cho, Kwangwook

PY - 2014/1/5

Y1 - 2014/1/5

N2 - The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.

AB - The microtubule-associated protein tau is a principal component of neurofibrillary tangles, and has been identified as a key molecule in Alzheimer's disease and other tauopathies. However, it is unknown how a protein that is primarily located in axons is involved in a disease that is believed to have a synaptic origin. To investigate a possible synaptic function of tau, we studied synaptic plasticity in the hippocampus and found a selective deficit in long-term depression (LTD) in tau knockout mice in vivo and in vitro, an effect that was replicated by RNAi knockdown of tau in vitro. We found that the induction of LTD is associated with the glycogen synthase kinase-3-mediated phosphorylation of tau. These observations demonstrate that tau has a critical physiological function in LTD.

U2 - 10.1098/rstb.2013.0144

DO - 10.1098/rstb.2013.0144

M3 - Article

SN - 1471-2970

VL - 369

JO - Philosophical Transactions of the Royal Society B

JF - Philosophical Transactions of the Royal Society B

IS - 1633

ER -

Microtubule-associated protein tau is essential for long-term depression in the hippocampus

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