Biology subjects

Sahoo, K.

Publications and source records attributed to Sahoo, K..

3 recordsLinked to original sources

bioRxiv2025

Cfap300 regulates the transdifferentiation of Corpuscle of Stannius cells in zebrafish

Stanniocalcin 1 (Stc1) is a hormone secreted by the Corpuscle of Stannius (CS) gland in teleost fish, including zebrafish, where it regulates calcium homeostasis. The CS gland forms by transdifferentiation of pronephric tubule epithelial cells at the distal early (DE) and distal late (DL) boundary. Although transdifferentiation is known in development and disease, the underlying mechanisms remain unclear. Here, we show that cfap300, a DNAAF implicated in primary ciliary dyskinesia (PCD), is essential for CS gland formation. TALEN-generated cfap300 mutants develop normally and show no nephron segmentation defects, but exhibit impaired CS development, which could be partially rescued by cfap300 mRNA injection. Further, cfap300 mutants display increased expression of cdh17 driven by Hnf1ba, which blocks CS precursor transdifferentiation. Knockdown of cdh17 or hnf1ba restores CS formation. These results uncover a Cfap300-Hnf1ba-Cdh17 pathway that regulates epithelial-to-endocrine transdifferentiation, revealing a novel, lineage-specific role for a DNAAF protein in endocrine organogenesis.

developmental biology↗

bioRxiv2025

Structure of YbbAP-TesA: a Type VII ABC transporter lipid-hydrolase complex

Type VII ABC transporters are ATP-powered membrane protein complexes that drive key biological processes in the bacterial cell envelope. In E. coli, three of the four Type VII ABC systems have been extensively characterised including: the FtsEX-EnvC cell division complex, the LolCDE-LolA lipoprotein trafficking machinery and the MacAB-TolC efflux pump. Here we describe a fourth E. coli Type VII ABC system, YbbAP-TesA, which combines a Type VII ABC transporter with a multifunctional hydrolytic enzyme. Structures of the complete YbbAP-TesA complex, and of YbbAP with and without bound ATP analogues, capture the long-range transmembrane conformational changes that are the hallmark of this ABC superfamilys mechanotransmission mechanism. We further show that YbbAP-TesA can hydrolyse a variety of ester and thioester substrates and experimentally confirm a constellation of active site residues in TesA. Our data suggests YbbAP has a role in extracting hydrophobic molecules from the inner membrane and presenting these to TesA for hydrolysis. The work extends collective knowledge of the remarkable diversity of the ABC superfamily and establishes a new function for Type VII ABC transporters in bacterial cells. Significance StatementType VII ABC transporters are unique to bacteria and play important roles in bacterial physiology including cell division, antibiotic resistance, siderophore secretion, antibiotic sensing, toxin secretion, biofilm regulation and lipoprotein trafficking. Here we identify a complex that combines an atypical Type VII ABC transporter (YbbAP) with a periplasmic lipid hydrolase (TesA). The YbbAP-TesA complex is structurally and functionally distinct from all known Type VII ABC transporter systems including FtsEX-EnvC, LolCDE-LolA, BceAB-BceS and MacAB-TolC. Structures suggest that YbbAP-TesA uses ATP-driven mechanotransmission to extract substrates from the inner membrane and hydrolyse them in the periplasmic space. The discovery and characterisation of YbbAP-TesA highlights the structural and functional diversity of Type VII ABC transporter complexes and suggests a new function for these proteins in the bacterial cell envelope.

microbiology↗

bioRxiv2021

Differential oxidative and pro-apoptotic response of cancer and normal cells to an anti-inflammatory agent CLEFMA

Selective killing of cancer cells by chemotherapy has been an age old challenge, but certain unique features of cancer cells allow discriminatory response between cancer and normal cells. The objectives of this study was to investigate pro-oxidant and apoptotic effects of CLEFMA, an anti-inflammatory compound with anticancer activity, in lung cancer cells versus normal lung fibroblasts and to establish its maximum tolerated dose (MTD) in mice. We found that CLEFMA preferentially induced reactive oxygen species (ROS)-mediated apoptosis in H441, H1650 and H226 cancer cells, but spared normal CCL151 and MRC9 fibroblasts. Immunoblotting studies revealed that CLEFMA-induced apoptosis is associated with p53 phosphorylation in cancer cells which was not observed in CLEFMA treated normal fibroblasts. CLEFMA showed no effect on NF-{kappa}B p-65 expression in the normal lung fibroblasts, whereas its translocation to nucleus was inhibited in cancer cells. Furthermore, CLEFMA treatment also inhibited the DNA-binding activity of NF-{kappa}B p65 in H441cancer cells, but not in normal CCL151 cells. Preclinical toxicology studies in CD31 mice showed that CLEFMA was not toxic when injected daily for 7 days or injected weekly for 4 weeks. Based on survival data, MTD of CLEFMA was estimated as 30 mg/kg bodyweight. We conclude that CLEFMA exploits the biochemical differences in cancer and normal cells and selectively induces ROS in cancer cells. Secondly, CLEFMA can be safely administered in vivo because its known dose necessary for in vivo efficacy as anti-inflammatory and anti-tumor agent (0.4 mg/kg) is 75 times lower than its MTD.

cancer biology↗