Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ptbp1 facilitates cytoskeletal organization through the mTOR-PKCα pathway in Sertoli cells thereby supporting spermatogenesis

ABSTRACT: Spermatogenesis is a highly coordinated process to produce mature spermatozoa. Somatic lineage Sertoli cells located in seminiferous tubule provide structural and paracrine support for spermatogenesis. Proper regulation of the Sertoli cell cytoskeleton dynamics is essential for this function; however, its regulatory mechanisms remain unclear. We show that the RNA-binding protein PTBP1 maintains cytoskeletal integrity in Sertoli cells via mTORC2 signaling. Sertoli cell–specific Ptbp1 deletion in mice results in germ cell loss, disrupted blood–testis barrier, and male infertility. Transcriptomic analysis of purified Sertoli cells revealed the dysregulation of cytoskeletal- and adhesion-related genes. RIP-seq demonstrated that PTBP1 binds to Rictor mRNA, which is a core mTORC2 component. PTBP1 loss reduced RICTOR protein levels and downstream PKCα activation, impairing the cytoskeletal structure. Rescue of cytoskeletal defects in PTBP1-deficient TM4 cells by constitutively active PKCα confirmed the functional relevance of the mTORC2–PKCα axis. These findings identify PTBP1 as a post-transcriptional regulator of mTORC2 signaling that supports Sertoli cell architecture and spermatogenesis, providing mechanistic insights into the regulation of male fertility.

ORGANISM(S): Mus musculus

PROVIDER: GSE295053 | GEO | 2025/12/31

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Ptbp1 facilitates cytoskeletal organization through the mTOR-PKCα pathway in Sertoli cells thereby supporting spermatogenesis

Project description:Ptbp1 facilitates cytoskeletal organization through the mTOR-PKCα pathway in Sertoli cells thereby supporting spermatogenesis

| PRJNA1252719 | ENA

Altered dermal architecture in PKCα-/- skin

Project description:Global gene expression analysis in PKCα-/- mouse skin reveals structural changes in the dermis and defective wound granulation tissue. The skin's mechanical integrity is maintained by an organised and robust dermal extracellular matrix (ECM). Resistance to mechanical disruption hinges primarily on homeostasis of the dermal collagen fibril architecture which is regulated, at least in part, by members of the small leucine-rich proteoglycan (SLRP) family. This array study presents data linking protein kinase C alpha (PKCα) to the regulated expression of multiple ECM components including SLRPs.

2016-01-20 | E-MTAB-3836 | biostudies-arrayexpress

PTBP1 mediates Sertoli cell actin cytoskeleton organization through regulating alternative splicing of actin regulators

Project description:Spermatogenesis is a biological process within the testis that produces haploid spermatozoa for the continuity of species. Sertoli cells are somatic cells in the seminiferous epithelium that orchestrate spermatogenesis. Cyclic reorganization of Sertoli cell actin cytoskeleton is vital for spermatogenesis but the underlying mechanism remains largely unclear. Here we report that RNA-binding protein PTBP1 controls Sertoli cell actin cytoskeleton reorganization by programming alternative splicing of actin cytoskeleton regulators. This splicing control enables ectoplasmic specializations, the actin-based adhesion junctions, to maintain the blood-testis barrier and support spermatid transport and transformation. Of particular, we show that PTBP1 promotes actin bundle formation by repressing the inclusion of exon 14 of Tnik, a kinase present at the ectoplasmic specialization. Our results thus reveal a novel mechanism wherein Sertoli cell actin cytoskeleton dynamics is controlled post-transcriptionally by utilizing functionally distinct isoforms of actin regulatory proteins and PTBP1 is a key player in generating such isoforms.

2024-07-31 | GSE267924 | GEO

Deletion of Rictor in brain and fat alters peripheral clock gene expression and increases blood pressure

Project description:The mammalian target of rapamycin complex 2 (mTORC2) contains the essential protein RICTOR and is activated by growth factors. mTORC2 in adipose tissue contributes to regulating glucose and lipid metabolism. In the perivascular adipose tissue (PVAT) mTORC2 ensures normal vascular reactivity by controlling expression of inflammatory molecules. To assess whether RICTOR/mTORC2 contributes to blood pressure regulation, we applied a radiotelemetry approach in control and Rictor knockout (RictoraP2KO) mice generated by using adipocyte protein-2 gene promoter-driven CRE recombinase to delete Rictor. 24 hour mean arterial pressure (MAP) was increased in RictoraP2KO mice, and the physiologic decline in MAP during the dark period impaired. In parallel, heart rate and locomotor activity were elevated during the dark period with a pattern similar to blood pressure changes. This phenotype was associated with mild cardiomyocyte hypertrophy, decreased cardiac natriuretic peptides (NPs) and NP receptor expression in adipocytes. Moreover, clock gene expression was dampened or phase-shifted in PVAT. No differences in clock gene expression were observed in the master clock suprachiasmatic nucleus (SCN), though Rictor gene expression was also lower in brain of RictoraP2KO mice. Thus, the present study underscores the importance of RICTOR/mTORC2 for interactions between vasculature, adipocytes and brain to tune physiological outcomes such as blood pressure and locomotion. Gene expression in PVAT of RictoraP2KO mice was compared to controls (Rictorfl/fl) mice.

2015-07-05 | E-GEOD-67077 | biostudies-arrayexpress

PKCα RNA-seq in t(4;14) cells

Project description:Multiple myeloma (MM) cells undergo metabolic reprogramming in response to a hypoxic and nutrient-deprived bone marrow microenvironment. However, it is unclear whether primary oncogenes in recurrent translocations drive metabolic heterogeneity that can present new vulnerabilities for therapeutic targeting. t(4;14) translocation leads to the universal overexpression of histone methyltransferase MMSET II that promotes plasma cell transformation through a global increase in H3K36me2. We identified PKCα as a novel epigenetic target that contributes to the oncogenic potential of MMSET II. RNA-sequencing of t(4;14) cell lines revealed a significant enrichment in the regulation of metabolic processes by PKCα, and the glycolytic gene, hexokinase 2 (HK2), is transcriptionally regulated by PKCα in a PI3K/Akt-dependent manner. Loss of PKCα displaces mitochondria-bound HK2 and reversed sensitivity towards the glycolytic blocker 3-Bromopyruvate. Additionally, we observed a metabolic shift to a less energetic state through the reduction in oxidative and glycolytic fluxes, resulting in an overall decrease in ATP production. We employed metabolomics and lactate emerged as a differential metabolite associated with PKCα. This conferred PKCα with immunomodulatory drug (IMiDs) resistance in a cereblon-independent manner and could be phenocopied by either overexpression of HK2 or direct supplementation of lactate. Altogether, we revealed novel insights into the epigenetic and metabolism crosstalk in MM and the opportunity for therapeutic intervention that leverages on the distinct metabolic program in t(4;14) myeloma.

2022-07-26 | GSE208739 | GEO

Expression data from mouse model using targeted deletion of hepatic RICTOR (Albumin-Cre Rictor LoxP/LoxP)

Project description:Recent work using mouse models has revealed that mTORC2, which unlike mTORC1 is not acutely sensitive to rapamycin, plays a key role in the regulation of organismal physiology. The substrates and pathways regulated by mTORC2 are at present relatively unknown Using a mouse model with a targeted deletion of hepatic RICTOR, we investigated the loss of mTORC2 on the murine liver transcriptome Rictor floxed (RKO) and control mice (n=4 per group) were fasted overnight, refed for 3 hr, then sacrificed. Livers were removed, rinsed in PBS, and flash frozen in liquid nitrogen. RNA was extracted and hybridized to Affymetrix Genechip Mouse Gene 1.0 ST arrays

2013-09-23 | E-GEOD-46515 | biostudies-arrayexpress

Effect of depletion of Rictor on gene expression during 3% DSS treatment of colonic epithelial cells.

Project description:mTORC2 signaling is critical for maintaining cellular metabolic hemostasis. We here report mTORC2 as a key regulator of mitochondrial oxidative phosphorylation in colonic epithelial cells. The depletion of Rictor results in serious colitis after 5 days of DSS treatment. In addition, loss of Rictor impaired OXPHOS activity and ATP production. Taken together, our data provide a molecular framework for mTORC2 signaling in colonic inflammation, in which mTORC2 positively regulate mitochondrial OXPHOS activity.

2025-12-18 | GSE250391 | GEO

Critical roles of Rictor/Sin1complexes in IFN-dependent Stat activation and generation of antiproliferative responses

Project description:We provide evidence that IFN-induced Stat-activation is defective in cells with targeted disruption of the Rictor gene, whose protein product is a key element of mTOR complex 2 (mTORC2). Our studies show that transient or stable knockdown of Rictor leads to decreased expression of several IFN-inducible genes that mediate important biological functions, including antiproliferative and pro-apoptotic responses. Rictor+/+ and Rictor-/- MEFs were treated with 2500 U/ml of mouse IFNα for 24 hours

2014-01-28 | E-GEOD-47896 | biostudies-arrayexpress

Deletion of Rictor in brain and fat alters peripheral clock gene expression and increases blood pressure

2015-07-05 | GSE67077 | GEO

Genome-wide analysis of gene expression in TM4 Sertoli cells following siRNA-mediated Gata4 inhibition

Project description:The effects of Gata4 inhibition on global gene expression in TM4 Sertoli cells was analyzed. Using microarray analysis we identified a set of genes that are downregulated or upregulated following siRNA-mediated silencing of Gata4 in the murine Sertoli cell line TM4. Among the downregulated genes were regulators of blood-testtis barrier function and lactate metabolism. TM4 cells were transfected with non-targeting (NT) siRNA and Gata4 siRNA respectively. 72h post transfection cells were lysed and RNA was extracted.

2016-03-17 | GSE74471 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data