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Polybasic RKKR motif in the linker region of lipid droplet (LD)-associated protein CIDEC inhibits LD fusion activity by interacting with acidic phospholipids.

ABSTRACT: Lipid droplets (LDs) are intracellular organelles and a central site for lipid synthesis, storage, and mobilization. The size of LDs reflects the dynamic regulation of lipid metabolism in cells. Previously, we found that cell death-inducing DFFA-like effector C (CIDEC) mediates LD fusion and growth by lipid transfer through LD-LD contact sites in adipocytes and hepatocytes. The CIDE-N domains of CIDEC molecules form homodimers, whereas the CIDE-C domain plays an important role in LD targeting and enrichment. Here, using targeted protein deletions and GFP expression coupled with fluorescence microscopy, we identified a polybasic RKKR motif in the linker region that connects the CIDE-N and CIDE-C domains of CIDEC and functions as a regulatory motif for LD fusion. We found that deletion of the linker region or mutation of the RKKR motif increases the formation of supersized LDs compared with LD formation in cells with WT CIDEC. This enhanced LD fusion activity required the interaction between CIDE-N domains. Mechanistically, we found that the RKKR motif interacts with acidic phospholipids via electrostatic attraction. Loss of this motif disrupted the protein-lipid interaction, resulting in enhanced lipid droplet fusion activity and thus formation of larger LDs. In summary, we have uncovered a CIDEC domain that regulates LD fusion activity, a finding that provides insights into the inhibitory regulation of LD fusion through CIDEC-lipid interactions.

SUBMITTER: Wang J

PROVIDER: S-EPMC6302180 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Polybasic RKKR motif in the linker region of lipid droplet (LD)-associated protein CIDEC inhibits LD fusion activity by interacting with acidic phospholipids.

Wang Jia J Yan Chengsong C Xu Chenqi C Chua Boon Tin BT Li Peng P Chen Feng-Jung FJ

The Journal of biological chemistry 20181025 50

Lipid droplets (LDs) are intracellular organelles and a central site for lipid synthesis, storage, and mobilization. The size of LDs reflects the dynamic regulation of lipid metabolism in cells. Previously, we found that cell death-inducing DFFA-like effector C (CIDEC) mediates LD fusion and growth by lipid transfer through LD-LD contact sites in adipocytes and hepatocytes. The CIDE-N domains of CIDEC molecules form homodimers, whereas the CIDE-C domain plays an important role in LD targeting an ...[more]

PMID: 30361435

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Dataset Information

Polybasic RKKR motif in the linker region of lipid droplet (LD)-associated protein CIDEC inhibits LD fusion activity by interacting with acidic phospholipids.

Publications

Polybasic RKKR motif in the linker region of lipid droplet (LD)-associated protein CIDEC inhibits LD fusion activity by interacting with acidic phospholipids.

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