Ask about this productRelated genes to: Rictor antibody
- Gene:
- RICTOR NIH gene
- Name:
- RPTOR independent companion of MTOR complex 2
- Previous symbol:
- -
- Synonyms:
- MGC39830, AVO3, PIA, KIAA1999
- Chromosome:
- 5p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2009-05-29
- Date modifiied:
- 2019-03-19
Related products to: Rictor antibody
Related articles to: Rictor antibody
- Type 1 diabetes (T1D) is a systemic metabolic disorder associated with male reproductive dysfunction. Given the pivotal role of actin cytoskeleton remodeling in spermatogenesis and sperm function, this study investigated the effects of T1D on actin-regulating pathways in rat testis and spermatozoa (SPZ). Adult Wistar rats were rendered diabetic by streptozotocin administration (65 mg/kg, i.p.). Testicular analysis revealed a reduced F-/G-actin ratio together with marked F-actin disorganization, consistent with altered actin cytoskeleton remodeling. To investigate the molecular mechanisms underlying these alterations, key regulators of actin dynamics were examined. Diabetic animals displayed impaired expression of EPS8, Fascin, N-WASP, and the ARP2/3 complex, suggesting altered regulation of actin assembly, bundling, and branching. Further analyses demonstrated dysregulation of signaling pathways governing cytoskeletal organization. Reduced levels of phosphorylated Disheveled-2, DAAM1, RhoA-GTP, and ROCK1 indicated impairment of the planar cell polarity pathway. In parallel, changes in LIMK1/cofilin phosphorylation supported abnormal regulation of actin filament turnover. Alterations in the RICTOR/PKC/MARCKS signaling pathway further highlighted defects in cytoskeletal control. Similar abnormalities were observed in mature SPZ, where altered F-actin distribution and DAAM1 localization suggested persistent cytoskeletal defects. Moreover, diabetic SPZ exhibited a reduced ability to undergo acrosome reaction, accompanied by altered MARCKS phosphorylation, highlighting defects in actin-dependent processes essential for sperm function and fertilizing capacity. These findings indicate that disruption of actin cytoskeleton dynamics may represent a major mechanism contributing to testicular and sperm abnormalities in T1D, providing new insights into the mechanisms underlying diabetes-associated male reproductive dysfunction. - Source: PubMed
Publication date: 2026/08/19
Ambruosi Maria RosariaBiasi AlessandraBoccella SerenaRomdhani IlefFalvo SaraGuida FrancescaMaione SabatinoMinucci SergioVenditti Massimo - Programmed cell death 4 (Pdcd4) is a well-established tumor suppressor as well as an inhibitor of protein translation. Although Pdcd4-mediated translational repression contributes to tumor suppression, emerging evidence suggests that Pdcd4 also exerts translation-independent functions. In this study, we found that Pdcd4 suppresses tumorigenesis through disrupting mTORC2 complex formation by binding with the rapamycin-insensitive companion of mTOR (Rictor), a core component of the mTORC2 complex. Using deletion mapping and site-directed mutagenesis, we defined the Rictor-binding domain of Pdcd4 and identified three critical residues, R105, K108, and R110, for this interaction. Co-immunoprecipitation and in vitro kinase assays demonstrated that Pdcd4 binding to Rictor disrupted mTORC2 complex assembly and inhibited its kinase activity. Reverse phase protein array analysis revealed that 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key regulator of glycolysis, was markedly upregulated in Pdcd4-knockdown cells. Restoration of wild-type Pdcd4, but not a Rictor-binding-deficient mutant, reduced PFKFB3 protein abundance by promoting ubiquitin-proteasome-mediated degradation. Functionally, Pdcd4-Rictor interaction suppressed glycolytic activity and inhibited tumor cell proliferation in cultured cells and xenograft models. Consistent with these findings, non-small cell lung cancer (NSCLC) tissues exhibited significantly elevated protein levels of Rictor and PFKFB3 compared with adjacent normal tissues, with a positive correlation between their expression. Collectively, these results demonstrate that Pdcd4-Rictor interaction disrupts mTORC2 signaling and downregulates PFKFB3, which plays a critical role in suppressing NSCLC growth and glycolysis. - Source: PubMed
Publication date: 2026/08/26
Wang QingXin YumengZokaei ElhamZeng LiangPiecoro DavaChen MinZhang YanquanYang Katie SWang ChiLiu XiaoqiYang Hsin-Sheng - Peripheral neuropathy affects over 18 million adults in the U.S. (Hicks et al 2021), but therapeutic outcomes are poor due to a lack of regenerative treatments. Development of novel, disease-modifying therapies is hindered by poor understanding of the mechanisms promoting axonal regeneration in peripheral neurons. Pten is a strong negative regulator of cell growth, and Pten-KO drives axonal regeneration in various neuronal subtypes potentially via downstream regulation of stability of the microtubule (MT) cytoskeleton, a vital component of axonal growth. While Pten-KO accelerates MT polymerization rates in the axonal growth cone, it remains unknown whether this action is dependent on mTORC1 or mTORC2 signaling, and whether regeneration under Pten-KO is dependent on MT activation. Here, we perform codeletions of either Raptor (mTORC1) or Rictor (mTORC2) alongside Pten-KO in mouse peripheral sensory neuron cultures of either sex to isolate the effects of each pathway on the MT cytoskeleton. We use Pten-KO to increase MT polymerization and neuronal outgrowth, and then show that suppression of mTORC2, but not mTORC1, is sufficient to reduce the accelerated MT polymerization and neuronal hypertrophy to wild-type levels. These results are specific to the axonal growth cone, and MT dynamics in the proximal axon shaft are not impacted by Pten-KO, mTORC1 suppression, or mTORC2 suppression. Our results help elucidate the mechanism by which Pten regulates the MT cytoskeleton and axonal outgrowth in peripheral sensory neurons, localize where this occurs in the axon, and highlight the MT cytoskeleton as a potential molecular target for regenerative therapies. Pten-KO promotes neuron growth, but Pten has several downstream effectors, and it is unclear which effectors drive axonal regeneration. One of these downstream targets is the microtubule cytoskeleton, which is vital for normal axonal growth and development. We demonstrate that Pten-KO increases MT polymerization rates in the growth cone, but not proximal shaft, in axons of peripheral sensory neurons. This effect is reversed by co-deletion of mTORC2, but not mTORC1, and the loss of mTORC2 primarily inhibits elongation of the distal axon, suggesting that the regulation of MT polymerization is specific to the growth cone. These results highlight MT dynamics in the axonal growth cone as a vital component of peripheral neuron regeneration and a potential therapeutic target. - Source: PubMed
Publication date: 2026/08/25
Evans SimoneReglewski JuliaRose HaleyLewis CaraNayak AnikaMinsky ColeMcNeil EvanKnowles BrizhaWang WeiLi MeijieLuikart Bryan WHong Jennifer - Miscarriage and abnormal embryonic development in women of advanced maternal age (AMA) are often associated with impaired decidualization. mTORC2 is an evolutionarily conserved protein kinase. As a core component of mTORC2, RICTOR has been implicated in nutrient sensing and is closely linked to implantation disorders; however, its role in regulating age-related decidualization disorders remains unreported. In this study, we identified pronounced decidualization defects in AMA foster mice, accompanied by a significant reduction in RICTOR in the decidual tissues of AMA women. Uterine-specific genetic deletion of Rictor in mice resulted in pregnancy loss and impaired decidualization. Notably, Rictor knockdown led to attenuated Akt3-FoxO1 signaling and impaired nuclear export of FoxO1. Molecular and histological analyses demonstrated that the specific RICTOR activator MHY1485 effectively rescued decidualization defects in vivo and in vitro. These findings indicate that RICTOR plays an essential role in the aging decidual microenvironment and may serve as a potential biomarker for uterine stromal cell decidualization. Furthermore, therapeutic activation of RICTOR represents a promising strategy to counteract senescent decidual impairment in AMA women and improve pregnancy outcomes. - Source: PubMed
Lin YifengSun JiweiYing YueLi DanYing YuewenShen XilinSun XiaoZhang DanWu YiqingZhang Runju - By integrating transcriptomics and network pharmacology, we systematically investigated the potential hemostatic mechanism of (BS). - Source: PubMed
Yang TaoXiong YanYang LingWang Xing-GangHuang YongFu Zhi-Li