Caspase-mediated nuclear pore complex trimming in cell differentiation and endoplasmic reticulum stress

Author:

Cho Ukrae H1ORCID,Hetzer Martin W12ORCID

Affiliation:

1. Molecular and Cell Biology Laboratory, Salk Institute for Biological Studies

2. Institute of Science and Technology Austria (IST Austria)

Abstract

During apoptosis, caspases degrade 8 out of ~30 nucleoporins to irreversibly demolish the nuclear pore complex. However, for poorly understood reasons, caspases are also activated during cell differentiation. Here, we show that sublethal activation of caspases during myogenesis results in the transient proteolysis of four peripheral Nups and one transmembrane Nup. ‘Trimmed’ NPCs become nuclear export-defective, and we identified in an unbiased manner several classes of cytoplasmic, plasma membrane, and mitochondrial proteins that rapidly accumulate in the nucleus. NPC trimming by non-apoptotic caspases was also observed in neurogenesis and endoplasmic reticulum stress. Our results suggest that caspases can reversibly modulate nuclear transport activity, which allows them to function as agents of cell differentiation and adaptation at sublethal levels.

Funder

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Institute of Neurological Disorders and Stroke

Glenn Foundation for Medical Research

NOMIS Stiftung

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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