Perilipin-4

{{Short description|Protein-coding gene in the species Homo sapiens}}

Perilipin 4, also known as S3-12, is a protein that in humans is encoded by the PLIN4 gene on chromosome 19.{{cite web | title = Entrez Gene: Perilipin 4 | url = https://www.ncbi.nlm.nih.gov/gene/729359 }}{{cite journal | vauthors = Cusano NE, Kiel DP, Demissie S, Karasik D, Adrienne Cupples L, Corella D, Gao Q, Richardson K, Yiannakouris N, Ordovas JM | title = A Polymorphism in a gene encoding Perilipin 4 is associated with height but not with bone measures in individuals from the Framingham Osteoporosis Study | journal = Calcified Tissue International | volume = 90 | issue = 2 | pages = 96–107 | date = February 2012 | pmc = 3628693 | doi = 10.1007/s00223-011-9552-7 | pmid = 22210160 }} It is highly expressed in white adipose tissue, with lower expression in heart, skeletal muscle, and brown adipose tissue.{{cite journal | vauthors = Brasaemle DL | title = Thematic review series: adipocyte biology. The perilipin family of structural lipid droplet proteins: stabilization of lipid droplets and control of lipolysis | journal = Journal of Lipid Research | volume = 48 | issue = 12 | pages = 2547–59 | date = December 2007 | doi = 10.1194/jlr.R700014-JLR200 | pmid = 17878492 | doi-access = free }} PLIN4 coats lipid droplets in adipocytes to protect them from lipases. The PLIN4 gene may be associated with insulin resistance and obesity risk.

Structure

= Gene =

The PLIN4 gene resides on chromosome 19 at the band 19p13.3 and contains 9 exons.

= Protein =

This protein belongs to the perilipin family and contains 27 33-amino acid approximate tandem repeats.{{UniProt Full|Q96Q06|PLIN4 - Perilipin-4 - Homo sapiens - PLIN4 gene & protein}} It is also one of the perilipin members of the PATS (PLIN, ADFP, TIP47, S3-12) family, which is named after structural proteins that share high amino acid sequence similarity and associate with lipid droplets. It shares a conserved C-terminal of 14 amino acid residues that folds into a hydrophobic cleft with other PATS members; however, it is missing the conserved N-terminal region of approximately 100 amino acid residues. Within the sequence of 33-amino acid repeats, PLIN4 contains a long stretch of imperfect 11-mer repeats predicted to form amphipathic helices with three helical turns per 11 amino acid residues. This 11-mer repeats tract is proposed to anchor the protein to the phospholipid monolayer of lipid droplets for its assembly, though no targeting sequence has yet been found in PLIN4.

Function

PLIN4 is a member of the perilipin family, a group of proteins that coat lipid droplets in adipocytes,{{cite journal | vauthors = Greenberg AS, Egan JJ, Wek SA, Garty NB, Blanchette-Mackie EJ, Londos C | title = Perilipin, a major hormonally regulated adipocyte-specific phosphoprotein associated with the periphery of lipid storage droplets | journal = The Journal of Biological Chemistry | volume = 266 | issue = 17 | pages = 11341–6 | date = June 1991 | doi = 10.1016/S0021-9258(18)99168-4 | pmid = 2040638 | doi-access = free }} the adipose tissue cells that are responsible for storing fat. Perilipin acts as a protective coating from the body’s natural lipases, such as hormone-sensitive lipase,{{cite web | url = http://www.scientificamerican.com/article.cfm?id=making-fat-proof-mice | title = Making Fat-proof Mice | author = Wong K | date = 2000-11-29 | publisher = Scientific American | access-date = 2009-05-22}} which break triglycerides into glycerol and free fatty acids for use in metabolism, a process called lipolysis.{{cite journal | vauthors = Wolins NE, Skinner JR, Schoenfish MJ, Tzekov A, Bensch KG, Bickel PE | title = Adipocyte protein S3-12 coats nascent lipid droplets | journal = The Journal of Biological Chemistry | volume = 278 | issue = 39 | pages = 37713–21 | date = September 2003 | pmid = 12840023 | doi = 10.1074/jbc.M304025200 | doi-access = free }} In humans, perilipin is expressed as 5 different isoforms; it is currently understood that the level of expression for each isoform is dependent on factors such as sex, body mass index, and level of endurance exercise.{{cite journal | vauthors = Peters SJ, Samjoo IA, Devries MC, Stevic I, Robertshaw HA, Tarnopolsky MA | title = Perilipin family (PLIN) proteins in human skeletal muscle: the effect of sex, obesity, and endurance training | journal = Applied Physiology, Nutrition, and Metabolism| volume = 37 | issue = 4 | pages = 724–35 | date = August 2012 | pmid = 22667335 | doi = 10.1139/h2012-059 }}

PLIN4 is hyperphosphorylated by PKA following β-adrenergic receptor activation. Phosphorylated perilipin changes conformation, exposing the stored lipids to hormone-sensitive lipase-mediated lipolysis. Although PKA also phosphorylates hormone-sensitive lipase, which can increase its activity, the more than 50-fold increase in fat mobilization (triggered by epinephrine) is primarily due to perilipin phosphorylation.

Clinical significance

The proteins in the Perilipin family are crucial regulators of lipid storage. PLIN4 expression is elevated in obese animals and humans.

The PLIN4 gene, along with PLIN2, PLIN3, and PLIN5, have been associated with variance in body-weight regulation and may be a genetic influence on obesity risk in humans.{{cite journal | vauthors = Soenen S, Mariman EC, Vogels N, Bouwman FG, den Hoed M, Brown L, Westerterp-Plantenga MS | title = Relationship between perilipin gene polymorphisms and body weight and body composition during weight loss and weight maintenance | journal = Physiology & Behavior | volume = 96 | issue = 4–5 | pages = 723–8 | date = March 2009 | pmid = 19385027 | doi = 10.1016/j.physbeh.2009.01.011 | s2cid = 24747708 }}

Interactions

PLIN4 has been shown to interact with Caspase 8 and Ubiquitin C.{{cite web | title = PLIN4 Results Summary | url = http://thebiogrid.org/609760|website=BioGrid | publisher = Tyerslab.com | access-date = 18 May 2015}}