Apoptotic stress induces Bax-dependent, caspase-independent redistribution of 
LINC complex nesprins

Lindenboim, Liora; Grozki, Dan; Amsalem-Zafran, Ayelet R.; Peña-Blanco, Aida; Gundersen, Gregg G.; Borner, Christoph; Hodzic, Didier; García-Sáez, Ana J.; Worman, Howard J.; Stein, Reuven

doi:10.1038/s41420-020-00327-6

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Apoptotic stress induces Bax-dependent, caspase-independent redistribution of LINC complex nesprins

MPS-Authors

There are no MPG-Authors in the publication available

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

s41420-020-00327-6.pdf
(Any fulltext), 3MB

Supplementary Material (public)

There is no public supplementary material available

Citation

Lindenboim, L., Grozki, D., Amsalem-Zafran, A. R., Peña-Blanco, A., Gundersen, G. G., Borner, C., et al. (2020). Apoptotic stress induces Bax-dependent, caspase-independent redistribution of LINC complex nesprins. Cell Death Discovery, 6: 90. doi:10.1038/s41420-020-00327-6.

Cite as: https://hdl.handle.net/21.11116/0000-000E-54A5-9

Abstract

The canonical function of Bcl-2 family proteins is to regulate mitochondrial membrane integrity. In response to apoptotic signals the multi-domain pro-apoptotic proteins Bax and Bak are activated and perforate the mitochondrial outer membrane by a mechanism which is inhibited by their interaction with pro-survival members of the family. However, other studies have shown that Bax and Bak may have additional, non-canonical functions, which include stress-induced nuclear envelope rupture and discharge of nuclear proteins into the cytosol. We show here that the apoptotic stimuli cisplatin and staurosporine induce a Bax/Bak-dependent degradation and subcellular redistribution of nesprin-1 and nesprin-2 but not nesprin-3, of the linker of nucleoskeleton and cytoskeleton (LINC) complex. The degradation and redistribution were caspase-independent and did not occur in Bax/Bak double knockout (DKO) mouse embryo fibroblasts (MEFs). Re-expression of Bax in Bax/Bak DKO MEFs restored stress-induced redistribution of nesprin-2 by a mechanism which requires Bax membrane localization and integrity of the α helices 5/6, and the Bcl-2 homology 3 (BH3) domain. We found that nesprin-2 interacts with Bax in close proximity to perinuclear mitochondria in mouse and human cells. This interaction requires the mitochondrial targeting and N-terminal region but not the BH3 domain of Bax. Our results identify nesprin-2 as a Bax binding partner and also a new function of Bax in impairing the integrity of the LINC complex.