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Mol Biol Cell. 2018 Dec 5:mbcE18040244. doi: 10.1091/mbc.E18-04-0244. [Epub ahead of print]

SUMOylation of Periplakin is critical for efficient re-organization of Keratin filament network.

Author information

1
Nups and SUMO Biology Group, Department of Biological Sciences, Indian Institute of Science Education and Research (IISER) Bhopal, Madhya Pradesh, India.
2
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 0QH, UK.
3
Department of Molecular Biology and Biotechnology, University of Sheffield, Sheffield S10 2TN, England, UK.

Abstract

The architecture of the cytoskeleton and its remodeling are tightly regulated by dynamic reorganization of keratin-rich intermediate filaments. Plakin family proteins associate with the network of intermediate filaments (IFs) and affect its reorganization during migration, differentiation, and response to stress. The smallest plakin, periplakin (PPL), interacts specifically with intermediate filament proteins K8, K18, and vimentin via its C-terminal linker domain. Here, we show that periplakin is SUMOylated at a conserved lysine in its linker domain (K1646) preferentially by SUMO1. Our data indicate that PPL SUMOylation is essential for the proper reorganization of the keratin IF network. Stresses perturbing intermediate-filament and cytoskeletal architecture induce hyper-SUMOylation of periplakin. Okadaic acid induced hyper-phosphorylation dependent collapse of the keratin IF network results in a similar hyper-SUMOylation of PPL. Strikingly, exogenous over-expression of a non-SUMOylatable periplakin mutant (K1646R) induced aberrant bundling and loose network interconnections of the keratin filaments. Time-lapse imaging of cells expressing the K1646R mutant showed the enhanced sensitivity of keratin filament collapse upon okadaic acid treatment. Our data identify an important regulatory role for periplakin SUMOylation in dynamic reorganization and stability of keratin IFs. Movie S1 Movie S1 Movie of GFP-PPL-C transfected HeLa cells, recorded for 3.5hr at 100X. Movie S2 Movie S2 Movie of GFP-PPL-C K1646R transfected HeLa cells, recorded for 3.5hr 100X. Movie S3 Movie S3 Movie of GFP-PPL-C transfected HeLa cells, recorded for 3.5hr in the presence of 0.5μM OA. Movie S4 Movie S4 Movie of GFP-PPL-C K1646R transfected HeLa cells, recorded for 3.5hr in the presence of 0.5μM OA. Movie S5 Movie S5 Movie of GFP-PPL-C transfected HeLa cells, recorded for 3.5hr at 100X in the presence of 0.25μM OA. Movie S6 Movie S6 Movie of GFP-PPL-C K1646R transfected HeLa cells, recorded for 3.5hr at 100X in the presence of 0.25μM OA. Movie S7 Movie S7 Movie of GFP-PPL-C transfected HEK293T cells, recorded for 2hr in the presence of 0.5μM OA. Movie S8 Movie S8 Movie of GFP-PPL-C K1646R transfected HEK293T cells, recorded for 2hr in the presence of 0.5μM OA. Movie S9 Movie S9 Movie of GFP-PPL-C transfected MCF7a cells, recorded for 2hr in the presence of 0.5μM OA. Movie S10 Movie S10 Movie of GFP-PPL-C K1646R transfected MCF7a cells, recorded for 2hr in the presence of 0.5μM OA.

PMID:
30516430
DOI:
10.1091/mbc.E18-04-0244

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