Perilipin-1

Key takeaways

Perilipin-1 belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Perilipin-1 to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Perilipin-1 from memory before moving on to harder problems.

Reference excerpt

Perilipin, also known as lipid droplet-associated protein, perilipin 1, or PLIN, is a protein that, in humans, is encoded by the PLIN gene. The perilipins are a family of proteins that associate with the surface of lipid droplets. Phosphorylation of perilipin is essential for the mobilization of fats in adipose tissue.

Perilipin family of proteins Perilipin is part of a gene family with six currently-known members. In vertebrates, closely related genes include adipophilin (also known as adipose differentiation-related protein or Perilipin 2), TIP47 (Perilipin 3), Perilipin 4 and Perilipin 5 (also called MLDP, LSDP5, or OXPAT). Insects express related proteins, LSD1 and LSD2, in fat bodies. The yeast Saccharomyces cerevisiae expresses PLN1 (formerly PET10), that stabilizes lipid droplets and aids in their assembly.

Evolution The perilipins are considered to have their origins in a common ancestral gene which, during the first and second vertebrate genome duplication, gave rise to six types of PLIN genes.

Composition and structure

Human perilipin Human perilipin-1 is composed by 522 amino acids, which add up to a molecular mass of 55.990 kDa. It presents an estimated number of 15 phosphorylation sites (residues 81, 85, 126, 130, 132, 137, 174, 299, 301, 382, 384, 408, 436, 497, 499 and 522) from which 3 -those in bold- have been suggested to be relevant for stimulated-lipolysis through PKA phosphorylation - they correspond respectively to PKA Phosphorylation sites 1, 5 and 6. A compositional bias of Glutamic acid can be found between residues 307 and 316. Its secondary structure has been suggested to be conformed exclusively by partially hydrophobic α-helixes, as well as the respective coils and bends.

Whereas perilipin-1 is coded by a single gene, alternative mRNA splicing processes can lead to three protein isoforms (Perilipin A, B and C). Both Perilipin A and B present common N-terminal regions, differing in the C-terminal ones. Concretely, beginning from the N-terminal of Perilipin-1, a PAT domain—characteristic of its protein family—can be found, followed by an also characteristic repeated sequence of 13 residues which form amphipathic helixes with an active role in linking membranes and a 4-helix bundle before the C-terminal carbon. In Perilipin A, lipophile nature is conferred by the slightly hydrophobic amino acids concentrated in the central 25% of the sequence, region that anchors the protein to the core of the lipid droplet.

Murine perilipin Serines occupying positions 81, 222, 276, 433, 492 and 517 act as phosphorylation sites -numbered from 1 to 6- for PKA, as well as several other threonines and serines which add up to 27 phosphorylation sites.

Function Perilipin is a protein that coats lipid droplets (LDs) in adipocytes, the fat-storing cells in adipose tissue. In fact, PLIN1 is greatly expressed in white adipocytes. It controls adipocyte lipid metabolism. It handles essential functions in the regulation of basal and hormonally stimulated lipolysis and also rises the formation of large LDs which implies an increase in the synthesis of triglycerides. In humans, Perilipin A is the most abundant protein associated with the adipocyte LDs and lower PLIN1 expression is related with higher rates of lipolysis. Under basal conditions, Perilipin acts as a protective coating of LDs from the body's natural lipases, such as hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL), which break triglycerides into glycerol and free fatty acids for use in lipid metabolism. In times of energy deficit, Perilipin is hyperphosphorylated by PKA following β-adrenergic receptor activation. Phosphorylated perilipin changes conformation, exposing the stored lipids to hormone-sensitive lipase-mediated lipolysis.

Modulator of adipocyte lipid metabolism Specifically, in the basal state Perilipin A allows a low level of basal lipolysis by reducing the access of cytosolic lipases to stored triacylglycerol in LDs. It is found at their surface in a complex with CGI-58, the co-activator of ATGL. ATGL might also be in this complex but it is quiescent. Under lipolytically stimulated conditions, PKA is activated and phosphorylates up to 6 Serine residues on Perilipin A (Ser81, 222, 276, 433, 492, and 517) and 2 on HSL (Ser659, and 660). Although PKA also phosphorylates HSL, which can increase its activity, the more than 50-fold increase in fat mobilization (triggered by epinephrine) is primarily due to Perilipin phosphorylation. Then, Phosphorylated HSL translocates to the LD surface and associates with Perilipin A and Adipocyte fatty acid-binding protein (AFABP). Consequently, HSL gains access to triacylglycerol (TAG) and diacylglycerol (DAG), substrates in LDs. Also, CGI-58 separates from the LD outer layer which leads to a redistribution of ATGL. In particular, ATGL interacts with Perilipin A through phosphorylated Ser517.

As a result, PKA phosphorylation implies an enriched colocation of HLS and ATGL which facilitates maximal lipolysis by the two lipases.

Clinical significance Perilipin is an important regulator of lipid storage. Both an overexpression or deficiency of the protein, caused by a mutation, lead to severe health issues.

Overexpression Perilipin expression is elevated in obese animals and humans. Polymorphisms in the human perilipin (PLIN) gene have been associated with variance in body-weight regulation and may be a genetic influence on obesity risk in humans. This protein can be modified by O-linked acetylglucosamine (O-GlNac) moieties and the enzyme that intervenes is O-GlcNAc transferase (OGT). An abundance of OGT obstructs lipolysis and benefits diet-induced obesity and whole-body insulin resistance. Studies also propose that an overexpression of adipose O-GlcNAc signaling is a molecular expression of obesity and diabetes in humans.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Perilipin-1

Start with the simplest possible case. Write down what Perilipin-1 claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Perilipin-1 before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Perilipin-1 ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Perilipin-1

In research: Perilipin-1 appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Perilipin-1 in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Perilipin-1 is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 15, Human proteins, Metabolism, so understanding it makes those chapters shorter.
In everyday life: Look for Perilipin-1 outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Perilipin-1 in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Perilipin-1 means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Perilipin-1 out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Perilipin-1 in simple terms?

Perilipin, also known as lipid droplet-associated protein, perilipin 1, or PLIN, is a protein that, in humans, is encoded by the PLIN gene. The perilipins are a family of proteins that associate with the surface of lipid droplets.

Why does Perilipin-1 matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Perilipin-1?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Perilipin-1.