PXD021969

PXD021969 is an original dataset announced via ProteomeXchange.

Title	Protein kinase A phosphorylation of perilipin 5 on serine 155 regulates liver lipolysis via interactions with adipose triglyceride lipase
Description	Perilipin (PLIN) 5 is a lipid droplet-associated protein that coordinates intracellular lipolysis in highly oxidative tissues and is thought to regulate lipid metabolism in response to phosphorylation by protein kinase A (PKA). We detected phosphorylation on S155, S161 and S163 of recombinant PLIN5 by PKA in vitro and identified S155 as a functionally important site for lipid metabolism. Expression of phosphorylation defective PLIN5 S155A in Plin5 null cells resulted in decreased rates of lipolysis and triglyceride-derived fatty acid oxidation compared with cells expressing wildtype PLIN5. These differences in lipid metabolism were not associated with differences in the cellular distribution of PLIN5. Rather, FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase (ATGL) at the lipid droplet, but not with the co-activator of ATGL, a-b hydrolase domain-containing 5 (ABHD5). Re-expression of PLIN5 S155A in the liver of Plin5 liver-specific null mice reduced lipolysis when compared to mice with wildtype PLIN5 re-expression, but this was not associated with changes in other parameters of hepatic lipid metabolism. Furthermore, glycemic control was impaired in mice with expression of PLIN5 S155A when compared with mice expressing PLIN5. Together, these studies demonstrate that PLIN5 S155 is required for PKA-mediated lipolysis and builds on the body of evidence demonstrating a critical role for PLIN5 in coordinating lipid and glucose metabolism.
HostingRepository	PRIDE
AnnounceDate	2021-03-12
AnnouncementXML	Submission_2021-03-11_22:28:47.648.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Ralf Schittenhelm
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	phosphorylated residue; monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-14 01:34:24	ID requested
1	2021-03-11 14:57:12	announced
⏵ 2	2021-03-11 22:28:48	announced	2021-03-12: Updated project metadata.

10.1194/JLR.RA120001126;

Keenan SN, De Nardo W, Lou J, Schittenhelm RB, Montgomery MK, Granneman JG, Hinde E, Watt MJ, Perilipin 5 S155 phosphorylation by PKA is required for the control of hepatic lipid metabolism and glycemic control. J Lipid Res, 62():100016(2021) [pubmed]

submitter keyword: Lipid metabolism, Perilipin, Lipid droplets, Lipase, Triglycerides, Fatty acid, Phosphorylation

Matthew J. Watt
contact affiliation	Department of Physiology, The University of Melbourne, Melbourne, Victoria, 3010 Australia
contact email	matt.watt@unimelb.edu.au
lab head
Ralf Schittenhelm
contact affiliation	Monash University
contact email	ralf.schittenhelm@monash.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD021969
     1. Label: PRIDE project
     2. Name: Protein kinase A phosphorylation of perilipin 5 on serine 155 regulates liver lipolysis via interactions with adipose triglyceride lipase