RPTOR

RPTOR Full Name

regulatory associated protein of MTOR, complex 1

RPTOR Introduction

RPTOR, also known as Raptor, is the regulatory-associated protein of mTORC1. mTORC1 is a protein kinase complex which serves as a master regulator of many processes within eukaryotic cells. The mTORC1 complex consists of several protein subunits including mTOR (the main kinase), RPTOR, mLST8 (GβL), PRAS40, and DEPTOR. RPTOR is an indispensable component of the mTORC1 complex that is critical for the structural integrity and biological activity of mTORC1. It mainly serves as a scaffold protein, recognizing and recruiting the downstream substrates of mTORC1 (such as S6K1 and 4E-BP1) so that mTOR kinase can phosphorylate those substrates and allow the initiation of the subsequent signal transduction.

Figure 1. Raptor and its orthologs. (Source: Yonezawa K, et al. 2004)

As an integral subunit of mTORC1, RPTOR's function is highly dependent on mTORC1. Consequently, mTORC1, via RPTOR, integrates and senses various intra- and extracellular environmental cues, including nutrient and energy levels and growth factors. mTORC1 is an important nutrient-sensitive factor and one of the key pathways responsible for the control of anabolic and catabolic processes. In the presence of high levels of nutrients and energy, mTORC1 is activated and recruits substrates that promote the biosynthesis of proteins, lipids and nucleotides for cell growth and proliferation, via RPTOR. At the same time, it inhibits autophagy, a catabolic process, to prevent cellular resources from being used for catabolism. As such, RPTOR and the mTORC1 complex in which it is a part, are important for modulating the cell's adaptive response to environmental changes. For example, in certain physiological settings like ensuring the survival and function of mouse germline stem cells, tight regulation of RPTOR has been shown to be critical.

In cancer, altered expression and/or mutation of RPTOR have been found in several tumors, such as lung cancer, colorectal cancer, and breast cancer. It has been found that high expression of RPTOR may promote tumor cell proliferation and survival, and has also been associated with brain metastasis in non-small cell lung cancer. In addition, differential methylation levels in the promoter region of the RPTOR gene have been associated with risk of breast cancer, suggesting that it may be regulated by epigenetic mechanisms in tumor development. As for neurological diseases, the research on RPTOR is also relatively extensive. In multiple studies, polymorphisms in the RPTOR gene have been found to be associated with decreased risk of Alzheimer's disease (AD). This was due to its functions of regulating neuronal autophagy, synaptic plasticity, and responses to viral encephalitis, while dysregulation of the mTOR pathway was thought to be one of the key mechanisms of neurodegenerative diseases. In addition, one large-scale genome-wide association study (GWAS) found that there were significant associations between the RPTOR gene and several psychiatric disorders, including schizophrenia and autism spectrum disorder.

Alternate Names for RPTOR

RPTOR; regulatory associated protein of MTOR, complex 1; KOG1; Mip1; regulatory-associated protein of mTOR; raptor; p150 target of rapamycin (TOR)-scaffold protein containing WD-repeats;

• 1. Yonezawa K, et al. Raptor, a binding partner of target of rapamycin. Biochem Biophys Res Commun. 2004 Jan 9;313(2):437-41.
  2. Kim DH, et al. Raptor and mTOR: subunits of a nutrient-sensitive complex. Curr Top Microbiol Immunol. 2004;279:259-70.