The Insulin/IGF signaling cascade modulates SUMOylation to regulate aging and proteostasis in C. elegans

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Abstract

Although aging-regulating pathways were discovered a few decades ago, it is not entirely clear how their activities are orchestrated, to govern lifespan and proteostasis at the organismal level. Here we utilized the nematode Caenorhabditis elegans to examine whether the alteration of aging, by reducing the activity of the Insulin/IGF signaling (IIS) cascade, affects protein SUMOylation. We found that IIS activity promotes the SUMOylation of the germline protein, CAR-1, thereby shortening lifespan and impairing proteostasis. In contrast, the expression of mutated CAR-1, that cannot be SUMOylated at residue 185, extends lifespan and enhances proteostasis. A mechanistic analysis indicated that CAR-1 mediates its aging-altering functions, at least partially, through the notch-like receptor glp-1. Our findings unveil a novel regulatory axis in which SUMOylation is utilized to integrate the aging-controlling functions of the IIS and of the germline and provide new insights into the roles of SUMOylation in the regulation of organismal aging.

Data availability

Mass Spectrometry data has been deposited at http://www.ebi.ac.uk/pride (Project accession: PXD010011).

The following data sets were generated

1. Moll L
2. Roitenberg N
3. Bajerano-Sagie M
4. Boocholez H
5. Carvalhal Marques F
6. Volovik Y
7. Elami T
8. Ahmed Siddiqui A
9. Grushko D
10. Biram A
11. Lampert B
12. Achache H
13. Ravid T
14. Tzur YB
15. Cohen E
(2018) The Insulin/IGF Signaling Cascade Modulates SUMOylation to Regulate Aging and Proteostasis in C. elegans
PRoteomics IDEntifications (PRIDE) database, PXD010011.

https://www.ebi.ac.uk/pride/archive/projects/PXD010011

Article and author information

Author details

Lorna Moll

Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Noa Roitenberg

Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Michal Bejerano-Sagie

Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Hana Boocholez

Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Filipa Carvalhal Marques

Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Yuli Volovik

Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Tayir Elami

Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Atif Ahmed Siddiqui

Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Danielle Grushko

Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Adi Biram

Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-6169-9861
Bar Lampert

Department of Genetics, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Hana Achache

Department of Genetics, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Tommer Ravid

Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Yonatan B Tzur

Department of Genetics, Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel

Competing interests
The authors declare that no competing interests exist.
Ehud Cohen

Department of Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

For correspondence
ehudc@ekmd.huji.ac.il

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-5552-7086

Funding

Israel Science Foundation (EC 981/16)

Hana Boocholez
Danielle Grushko
Ehud Cohen

Israel Science Foundation (YBT 2090/15)

Bar Lampert
Yonatan B Tzur

Israel Science Foundation (YBT 1283/15)

Bar Lampert
Yonatan B Tzur

European Research Council (EC 281010)

Lorna Moll
Noa Roitenberg
Michal Bejerano-Sagie
Filipa Carvalhal Marques
Yuli Volovik
Tayir Elami
Danielle Grushko
Ehud Cohen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.