MLKL Forms Cation Channels

Overview

Journal Cell Res

Specialty Cell Biology

Date 2016 Apr 2

PMID 27033670

Citations 99

Authors

Bingqing Xia

Sui Fang

Xueqin Chen

Hong Hu

Peiyuan Chen

Huayi Wang

Zhaobing Gao

Affiliations

Soon will be listed here.

Abstract

The mixed lineage kinase domain-like (MLKL) protein is a key factor in tumor necrosis factor-induced necroptosis. Recent studies on necroptosis execution revealed a commitment role of MLKL in membrane disruption. However, our knowledge of how MLKL functions on membrane remains very limited. Here we demonstrate that MLKL forms cation channels that are permeable preferentially to Mg(2+) rather than Ca(2+) in the presence of Na(+) and K(+). Moreover, the N-terminal domain containing six helices (H1-H6) is sufficient to form channels. Using the substituted cysteine accessibility method, we further determine that helix H1, H2, H3, H5 and H6 are transmembrane segments, while H4 is located in the cytoplasm. Finally, MLKL-induced membrane depolarization and cell death exhibit a positive correlation to its channel activity. The Mg(2+)-preferred permeability and five transmembrane segment topology distinguish MLKL from previously identified Mg(2+)-permeable channels and thus establish MLKL as a novel class of cation channels.

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