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Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue

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Harvard

Lundh, M, Petersen, PS, Isidor, MS, Kazoka-Sørensen, DN, Plucińska, K, Shamsi, F, Ørskov, C, Tozzi, M, Brown, EL, Andersen, E, Ma, T, Müller, U, Barrès, R, Kristiansen, VB, Gerhart-Hines, Z, Tseng, Y-H & Emanuelli, B 2019, 'Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue' EMBO Reports, bind 20, nr. 8, e48216. https://doi.org/10.15252/embr.201948216

APA

Lundh, M., Petersen, P. S., Isidor, M. S., Kazoka-Sørensen, D. N., Plucińska, K., Shamsi, F., ... Emanuelli, B. (2019). Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue. EMBO Reports, 20(8), [e48216]. https://doi.org/10.15252/embr.201948216

CBE

Lundh M, Petersen PS, Isidor MS, Kazoka-Sørensen DN, Plucińska K, Shamsi F, Ørskov C, Tozzi M, Brown EL, Andersen E, Ma T, Müller U, Barrès R, Kristiansen VB, Gerhart-Hines Z, Tseng Y-H, Emanuelli B. 2019. Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue. EMBO Reports. 20(8). https://doi.org/10.15252/embr.201948216

MLA

Vancouver

Lundh M, Petersen PS, Isidor MS, Kazoka-Sørensen DN, Plucińska K, Shamsi F o.a. Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue. EMBO Reports. 2019 aug;20(8). e48216. https://doi.org/10.15252/embr.201948216

Author

Lundh, Morten ; Petersen, Patricia Ss ; Isidor, Marie S ; Kazoka-Sørensen, Dolly Nm ; Plucińska, Kaja ; Shamsi, Farnaz ; Ørskov, Cathrine ; Tozzi, Marco ; Brown, Erin L ; Andersen, Emil ; Ma, Tao ; Müller, Ulrich ; Barrès, Romain ; Kristiansen, Viggo B ; Gerhart-Hines, Zachary ; Tseng, Yu-Hua ; Emanuelli, Brice. / Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue. I: EMBO Reports. 2019 ; Bind 20, Nr. 8.

Bibtex

@article{0450fb38ef1a4ace90e18b93a5d570c8,
title = "Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue",
abstract = "Insulin orchestrates metabolic homeostasis through a complex signaling network for which the precise mechanisms controlling its fine-tuning are not completely understood. Here, we report that Afadin, a scaffold protein, is phosphorylated on S1795 (S1718 in humans) in response to insulin in adipocytes, and this phosphorylation is impaired with obesity and insulin resistance. In turn, loss of Afadin enhances the response to insulin in adipose tissues via upregulation of the insulin receptor protein levels. This happens in a cell-autonomous and phosphorylation-dependent manner. Insulin-stimulated Afadin-S1795 phosphorylation modulates Afadin binding with interaction partners in adipocytes, among which HDAC6 preferentially interacts with phosphorylated Afadin and acts as a key intermediate to suppress insulin receptor protein levels. Adipose tissue-specific Afadin depletion protects against insulin resistance and improves glucose homeostasis in diet-induced obese mice, independently of adiposity. Altogether, we uncover a novel insulin-induced cellular feedback mechanism governed by the interaction of Afadin with HDAC6 to negatively control insulin action in adipocytes, which may offer new strategies to alleviate insulin resistance.",
author = "Morten Lundh and Petersen, {Patricia Ss} and Isidor, {Marie S} and Kazoka-S{\o}rensen, {Dolly Nm} and Kaja Plucińska and Farnaz Shamsi and Cathrine {\O}rskov and Marco Tozzi and Brown, {Erin L} and Emil Andersen and Tao Ma and Ulrich M{\"u}ller and Romain Barr{\`e}s and Kristiansen, {Viggo B} and Zachary Gerhart-Hines and Yu-Hua Tseng and Brice Emanuelli",
note = "{\circledC} 2019 The Authors.",
year = "2019",
month = "8",
doi = "10.15252/embr.201948216",
language = "English",
volume = "20",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "8",

}

RIS

TY - JOUR

T1 - Afadin is a scaffold protein repressing insulin action via HDAC6 in adipose tissue

AU - Lundh, Morten

AU - Petersen, Patricia Ss

AU - Isidor, Marie S

AU - Kazoka-Sørensen, Dolly Nm

AU - Plucińska, Kaja

AU - Shamsi, Farnaz

AU - Ørskov, Cathrine

AU - Tozzi, Marco

AU - Brown, Erin L

AU - Andersen, Emil

AU - Ma, Tao

AU - Müller, Ulrich

AU - Barrès, Romain

AU - Kristiansen, Viggo B

AU - Gerhart-Hines, Zachary

AU - Tseng, Yu-Hua

AU - Emanuelli, Brice

N1 - © 2019 The Authors.

PY - 2019/8

Y1 - 2019/8

N2 - Insulin orchestrates metabolic homeostasis through a complex signaling network for which the precise mechanisms controlling its fine-tuning are not completely understood. Here, we report that Afadin, a scaffold protein, is phosphorylated on S1795 (S1718 in humans) in response to insulin in adipocytes, and this phosphorylation is impaired with obesity and insulin resistance. In turn, loss of Afadin enhances the response to insulin in adipose tissues via upregulation of the insulin receptor protein levels. This happens in a cell-autonomous and phosphorylation-dependent manner. Insulin-stimulated Afadin-S1795 phosphorylation modulates Afadin binding with interaction partners in adipocytes, among which HDAC6 preferentially interacts with phosphorylated Afadin and acts as a key intermediate to suppress insulin receptor protein levels. Adipose tissue-specific Afadin depletion protects against insulin resistance and improves glucose homeostasis in diet-induced obese mice, independently of adiposity. Altogether, we uncover a novel insulin-induced cellular feedback mechanism governed by the interaction of Afadin with HDAC6 to negatively control insulin action in adipocytes, which may offer new strategies to alleviate insulin resistance.

AB - Insulin orchestrates metabolic homeostasis through a complex signaling network for which the precise mechanisms controlling its fine-tuning are not completely understood. Here, we report that Afadin, a scaffold protein, is phosphorylated on S1795 (S1718 in humans) in response to insulin in adipocytes, and this phosphorylation is impaired with obesity and insulin resistance. In turn, loss of Afadin enhances the response to insulin in adipose tissues via upregulation of the insulin receptor protein levels. This happens in a cell-autonomous and phosphorylation-dependent manner. Insulin-stimulated Afadin-S1795 phosphorylation modulates Afadin binding with interaction partners in adipocytes, among which HDAC6 preferentially interacts with phosphorylated Afadin and acts as a key intermediate to suppress insulin receptor protein levels. Adipose tissue-specific Afadin depletion protects against insulin resistance and improves glucose homeostasis in diet-induced obese mice, independently of adiposity. Altogether, we uncover a novel insulin-induced cellular feedback mechanism governed by the interaction of Afadin with HDAC6 to negatively control insulin action in adipocytes, which may offer new strategies to alleviate insulin resistance.

U2 - 10.15252/embr.201948216

DO - 10.15252/embr.201948216

M3 - Journal article

VL - 20

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

IS - 8

M1 - e48216

ER -

ID: 57520363