RPTOR

Key takeaways

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

Reference excerpt

Regulatory-associated protein of mTOR also known as raptor or KIAA1303 is an adapter protein that is encoded in humans by the RPTOR gene. The RPTOR protein is a component of the protein complex mTORC1, a nutrient sensor that promotes cell growth and anabolic reactions in response to nutrients or growth factors. Inside of mTORC1, RPTOR has two major known adaptor functions. In particular, it interacts with Rag GTPases (RRAGA, RRAGB, RRAGC and/or RRAGD), recruiting the complex to lysosome membranes, and also binds to TOS motif-containing proteins, and directs them to the complex’s phosphorylating domain. Two mRNAs from the gene have been identified that encode proteins of 1335 (isoform 1) and 1177 (isoform 2) amino acids long.

Gene and expression The human gene is located on human chromosome 17 with location of the cytogenic band at 17q25.3.

Location RPTOR is highly expressed in skeletal muscle and is somewhat less present in brain, lung, small intestine, kidney, and placenta tissue. Isoform 3 is widely expressed and most highly expressed in the nasal mucosa and pituitary. The lowest levels occur in the spleen. In the cell, RPTOR is present in cytoplasm, lysosomes, and cytoplasmic granules. Amino acid availability determines RPTOR targeting to lysosomes. In stressed cells, RPTOR associates with SPAG5 and accumulates in stress granules, which significantly reduces its presence in lysosomes.

Function RPTOR encodes part of a signaling pathway regulating cell growth which responds to nutrient and insulin levels. RPTOR is an evolutionarily conserved protein with multiple roles in the mTOR pathway. The adapter protein and mTOR kinase form a stoichiometric complex. The encoded protein also associates with eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase. It upregulates S6 kinase, the downstream effector ribosomal protein, and it downregulates the mTOR kinase. RPTOR also has a positive role in maintaining cell size and mTOR protein expression. The association of mTOR and RPTOR is stabilized by nutrient deprivation and other conditions which suppress the mTOR pathway. Multiple transcript variants exist for this gene which encode different isoforms.

Structure RPTOR is a 150 kDa mTOR binding protein that is part of the mammalian target of rapamycin complex 1 (mTORC1). This complex contains mTOR, MLST8, RPTOR, AKT1S1/PRAS40, and DEPTOR. mTORC1 both binds to and is inhibited by FKBP12-rapamycin. mTORC1 activity is upregulated by mTOR and MPAK8 by insulin-stimulated phosphorylation at Ser-863. MAPK8 also causes phosphorylation at Ser-696, Thr-706, and Ser-863 as a result of osmotic stress. AMPK causes phosphorylation in the event of nutrient starvation and promotes 14-3-3 binding to raptor, which downregulates the mTORC1 complex. RPS6KA1 stimulates mTORC1 activity by phosphorylating at Ser-719, Ser-721, and Ser-722 as a response to growth factors.

Interactions mTORC1 binds to and is inhibited by FKBP12-rapamycin RPTOR binds to 4EBP1 and RPS6KB1 directly whether or not it is associated with mTOR RPTOR binds to poorly phosphorylated or non-phosphorylated EIF4EBP1 preferentially, which is important for mTOR to be able to catalyze phosphorylation. RPTOR interacts with ULK1. This interaction depends on nutrients and is reduced in the case of starvation. When RPTOR is phosphorylated by AMPK, it interacts with 14-3-3 protein and inhibits its activity. RPTOR interacts with SPAG5, which competes with mTOR for binding RPTOR and causes decreased mTORC1 formation. RPTOR interacts with G3BP1. Oxidative stress increases the formation of the complex formed with RPTOR, G3BP1, and SPAG5 RPTOR has also been shown to interact with:

FKBP1A, P70-S6 Kinase 1 RHEB, RICTOR, and mammalian target of rapamycin (mTOR),

Clinical significance

Signaling in cancer The clinical significance of RPTOR is primarily due to its involvement in the mTOR pathway, which plays roles in mRNA translation, autophagy, and cell growth. Mutations in the PTEN tumor suppressor gene are the best known genetic deficiencies in cancer which affect mTOR signaling. These mutations are frequently found in a very large variety of cancers, including prostate, breast, lung, bladder, melanoma, endometrial, thyroid, brain, and renal carcinomas. PTEN inhibits the lipid-kinase activity of class I PtdIns3Ks, which phosphorylate PtdIns(4,5)P2 to create PtdIns(3,4,5)P3 (PIP3). PIP3 is a membrane-docking site for AKT and PDK1. In turn, active PDK1, along with mTORC1, phosphorylates S6K in the part of the mTOR pathway which promotes protein synthesis and cell growth. The mTOR pathway has also been found to be involved in aging. Studies with C. elegans, fruitflies, and mice have shown that the lifespan of the organism is significantly increased by inhibiting mTORC1. mTORC1 phosphorylates Atg13 and stops it from forming the ULK1 kinase complex. This inhibits autophagy, the major degradation pathway in eukaryotic cells. Because mTORC1 inhibits autophagy and stimulates cell growth, it can cause damaged proteins and cell structures to accumulate. For this reason, dysfunction in the process of autophagy can contribute to several diseases, including cancer. The mTOR pathway is important in many cancers. In cancer cells, astrin is required to suppress apoptosis during stress. Astrin recruits RPTOR to stress granules, inhibiting mTORC1 association and preventing apoptosis induced by mTORC1 hyperactivation. Because astrin is frequently upregulated in tumors, it is a potential target to sensitize tumors to apoptosis through the mTORC1 pathway. RPTOR is overexpressed in pituitary adenoma, and its expression increases with tumor staging. RPTOR could be valuable in the prediction and prognosis of pituitary adenoma due to this correlation between protein expression and the growth and invasion of the tumor.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with RPTOR

Start with the simplest possible case. Write down what RPTOR 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 RPTOR 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 RPTOR 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 RPTOR

In research: RPTOR 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 RPTOR 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: RPTOR is common in secondary-school and first-year university syllabi. It links to neighbouring topics Genes on human chromosome 17, Genes on human chromosome 3, Tor signaling pathway, so understanding it makes those chapters shorter.
In everyday life: Look for RPTOR 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 RPTOR in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what RPTOR 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 RPTOR out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is RPTOR in simple terms?

Regulatory-associated protein of mTOR also known as raptor or KIAA1303 is an adapter protein that is encoded in humans by the RPTOR gene. The RPTOR protein is a component of the protein complex mTORC1, a nutrient sensor that promotes cell growth and anabolic reactions in response to nutrients or gr…

Why does RPTOR 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 RPTOR?

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 RPTOR.