Golgi organization is regulated by proteasomal degradation

Avital Eisenberg-Lerner; Ron Benyair; Noa Hizkiahou; Neta Nudel; Roey Maor; Matthias P. Kramer; Merav D. Shmueli; Inbal Zigdon; Marina Cherniavsky Lev; Adi Ulman; Jitka Yehudith Sagiv; Molly Dayan; Mercedes Rosenwald; Idit Shachar; Jie Li; Yanzhuang Wang; Nili Dezorella; Suman Khan; Ziv Porat; Eyal Shimoni; Ori Avinoam; Yifat Merbl

doi:10.1038/s41467-019-14038-9

Golgi organization is regulated by proteasomal degradation

Avital Eisenberg-Lerner, Ron Benyair, Noa Hizkiahou, Neta Nudel, Roey Maor, Matthias P. Kramer, Merav D. Shmueli, Inbal Zigdon, Marina Cherniavsky Lev, Adi Ulman, Jitka Yehudith Sagiv, Molly Dayan, Mercedes Rosenwald, Idit Shachar, Jie Li, Yanzhuang Wang, Nili Dezorella, Suman Khan, Ziv Porat, Eyal ShimoniOri Avinoam, Yifat Merbl

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

Abstract

The Golgi is a dynamic organelle whose correct assembly is crucial for cellular homeostasis. Perturbations in Golgi structure are associated with numerous disorders from neurodegeneration to cancer. However, whether and how dispersal of the Golgi apparatus is actively regulated under stress, and the consequences of Golgi dispersal, remain unknown. Here we demonstrate that 26S proteasomes are associated with the cytosolic surface of Golgi membranes to facilitate Golgi Apparatus-Related Degradation (GARD) and degradation of GM130 in response to Golgi stress. The degradation of GM130 is dependent on p97/VCP and 26S proteasomes, and required for Golgi dispersal. Finally, we show that perturbation of Golgi homeostasis induces cell death of multiple myeloma in vitro and in vivo, offering a therapeutic strategy for this malignancy. Taken together, this work reveals a mechanism of Golgi-localized proteasomal degradation, providing a functional link between proteostasis control and Golgi architecture, which may be critical in various secretion-related pathologies.

Original language	English
Article number	409
Number of pages	14
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-14038-9
State	Published - 21 Jan 2020

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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https://harvester-2-eu.services.rm.elsevier.com/ws/6ced8d3b-d9ff-4f31-979a-0647230ba9f4/1815c317-615c-4123-822c-c2c538e6ff99/ws/files/111307912/ym_NatCommun_GolgiOrganization_PV2020.pdfLicense: CC BY

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Eisenberg-Lerner, A., Benyair, R., Hizkiahou, N., Nudel, N., Maor, R., Kramer, M. P., Shmueli, M. D., Zigdon, I., Lev, M. C., Ulman, A., Sagiv, J. Y., Dayan, M., Rosenwald, M., Shachar, I., Li, J., Wang, Y., Dezorella, N., Khan, S., Porat, Z., ... Merbl, Y. (2020). Golgi organization is regulated by proteasomal degradation. Nature Communications, 11(1), Article 409. https://doi.org/10.1038/s41467-019-14038-9

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title = "Golgi organization is regulated by proteasomal degradation",

abstract = "The Golgi is a dynamic organelle whose correct assembly is crucial for cellular homeostasis. Perturbations in Golgi structure are associated with numerous disorders from neurodegeneration to cancer. However, whether and how dispersal of the Golgi apparatus is actively regulated under stress, and the consequences of Golgi dispersal, remain unknown. Here we demonstrate that 26S proteasomes are associated with the cytosolic surface of Golgi membranes to facilitate Golgi Apparatus-Related Degradation (GARD) and degradation of GM130 in response to Golgi stress. The degradation of GM130 is dependent on p97/VCP and 26S proteasomes, and required for Golgi dispersal. Finally, we show that perturbation of Golgi homeostasis induces cell death of multiple myeloma in vitro and in vivo, offering a therapeutic strategy for this malignancy. Taken together, this work reveals a mechanism of Golgi-localized proteasomal degradation, providing a functional link between proteostasis control and Golgi architecture, which may be critical in various secretion-related pathologies.",

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Eisenberg-Lerner, A, Benyair, R, Hizkiahou, N, Nudel, N, Maor, R, Kramer, MP, Shmueli, MD, Zigdon, I, Lev, MC, Ulman, A, Sagiv, JY, Dayan, M, Rosenwald, M, Shachar, I, Li, J, Wang, Y, Dezorella, N, Khan, S, Porat, Z, Shimoni, E, Avinoam, O & Merbl, Y 2020, 'Golgi organization is regulated by proteasomal degradation', Nature Communications, vol. 11, no. 1, 409. https://doi.org/10.1038/s41467-019-14038-9

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T1 - Golgi organization is regulated by proteasomal degradation

AU - Eisenberg-Lerner, Avital

AU - Benyair, Ron

AU - Hizkiahou, Noa

AU - Nudel, Neta

AU - Maor, Roey

AU - Kramer, Matthias P.

AU - Shmueli, Merav D.

AU - Zigdon, Inbal

AU - Lev, Marina Cherniavsky

AU - Ulman, Adi

AU - Sagiv, Jitka Yehudith

AU - Dayan, Molly

AU - Rosenwald, Mercedes

AU - Shachar, Idit

AU - Li, Jie

AU - Wang, Yanzhuang

AU - Dezorella, Nili

AU - Khan, Suman

AU - Porat, Ziv

AU - Shimoni, Eyal

AU - Avinoam, Ori

AU - Merbl, Yifat

PY - 2020/1/21

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N2 - The Golgi is a dynamic organelle whose correct assembly is crucial for cellular homeostasis. Perturbations in Golgi structure are associated with numerous disorders from neurodegeneration to cancer. However, whether and how dispersal of the Golgi apparatus is actively regulated under stress, and the consequences of Golgi dispersal, remain unknown. Here we demonstrate that 26S proteasomes are associated with the cytosolic surface of Golgi membranes to facilitate Golgi Apparatus-Related Degradation (GARD) and degradation of GM130 in response to Golgi stress. The degradation of GM130 is dependent on p97/VCP and 26S proteasomes, and required for Golgi dispersal. Finally, we show that perturbation of Golgi homeostasis induces cell death of multiple myeloma in vitro and in vivo, offering a therapeutic strategy for this malignancy. Taken together, this work reveals a mechanism of Golgi-localized proteasomal degradation, providing a functional link between proteostasis control and Golgi architecture, which may be critical in various secretion-related pathologies.

AB - The Golgi is a dynamic organelle whose correct assembly is crucial for cellular homeostasis. Perturbations in Golgi structure are associated with numerous disorders from neurodegeneration to cancer. However, whether and how dispersal of the Golgi apparatus is actively regulated under stress, and the consequences of Golgi dispersal, remain unknown. Here we demonstrate that 26S proteasomes are associated with the cytosolic surface of Golgi membranes to facilitate Golgi Apparatus-Related Degradation (GARD) and degradation of GM130 in response to Golgi stress. The degradation of GM130 is dependent on p97/VCP and 26S proteasomes, and required for Golgi dispersal. Finally, we show that perturbation of Golgi homeostasis induces cell death of multiple myeloma in vitro and in vivo, offering a therapeutic strategy for this malignancy. Taken together, this work reveals a mechanism of Golgi-localized proteasomal degradation, providing a functional link between proteostasis control and Golgi architecture, which may be critical in various secretion-related pathologies.

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SN - 2041-1723

VL - 11

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 409

ER -

Golgi organization is regulated by proteasomal degradation

Abstract

All Science Journal Classification (ASJC) codes

UN SDGs

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