Biology subjects

Rangaraj, N.

Publications and source records attributed to Rangaraj, N..

3 recordsLinked to original sources

bioRxiv2023

Transferrin-induced signaling through transferrin receptor and AKT kinase mediates formation of Rab8- and MICAL-L1-positive tubules involved in receptor recycling

Transferrin and its receptor play an important role in iron homeostasis. Binding of transferrin to its receptor (TFRC, transferrin receptor protein 1) initiates endocytic trafficking and subsequent recycling of TFRC to the plasma membrane. RAB8-positive tubules emanating from the endocytic recycling compartment play an important role in receptor recycling. However, the signaling pathways or mechanisms that mediate formation of RAB8-positive tubules are not clear. Here, we have investigated the role of transferrin-induced signaling in the regulation of RAB8- and MICAL-L1-positive tubules. Addition of transferrin to the serum starved HeLa cells resulted in enhanced recruitment of RAB8 as well as MICAL-L1 to the tubules, which was mediated by TFRC. Dynasore, an inhibitor of dynamin and endocytosis, completely blocked transferrin-induced formation of RAB8/MICAL-L1-positive tubules. RAB8 showed strong colocalization with MICAL-L1 on the tubules. Blocking of SRC or AKT kinase activity by specific inhibitors abolished transferrin-induced recruitment of RAB8 and MICAL-L1 to the tubules. Recycling of transferrin receptor was inhibited by blocking of AKT activity. TBC1D17, a GTPase activating protein for RAB8, inhibited RAB8/MICAL-L1-positive tubule formation. A phospho-mimicking mutant S366D of TBC1D17 did not inhibit formation of RAB8-positive tubules. Overall, these results show that transferrin induces TFRC mediated signaling dependent on endocytosis that is essential for the formation of RAB8- and MICAL-L1-positive tubules involved in recycling of transferrin receptor. Our results also show that AKT regulates transferrin-induced formation of RAB8- and MICAL-L1-positive tubules, which might be mediated by phosphorylation of TBC1D17.

cell biology↗

bioRxiv2019

Preparation of Organ Scaffolds by Decellularization of Pancreas and Re-functionalization

Extracellular matrix of each tissue is unique in composition, architecture and finer details that support the very identity of the organ by regulating the status/character of the cells within it. Tissue engineering centers around creating a niche similar to the natural one, with a purpose of developing an organ/oid. In this study, whole organ decellularization of pancreas was attempted followed by reseeding it with adult mesenchymal stem cells. Decellularization completely removes cells leaving behind extracellular matrix rich scaffold. After reseeding, mesenchymal stem cells differentiate into pancreas specific cells. Upon transplantation of recellularized pancreas in streptozotocin induced diabetic mice, this organ was capable of restoring its histomorphology and normal functioning. Restoration of endocrine islets, the exocrine acinar region, and vascular network was seen in transplanted pancreas. The entire process of functional recovery took about 20 days when the mice demonstrated glucoregulation, though none achieved gluconormalization. Transplanted mice upon feeding show insulin and c-peptide in circulation. This process demonstrates that natural scaffolds of soft organs can be refunctionalized using recipients cells to counter immune problems arising due to organ transplantation.

cell biology↗

bioRxiv2018

Y chromosomal noncoding RNA regulates autosomal gene expression via piRNAs in mouse testis

Majority of the genes expressed during spermatogenesis are autosomal. Mice with different deletions of Yq show sub-fertility, sterility and sperm abnormalities. The connection between Yq deletion and autosomal gene regulation is not well understood. We describe a novel mouse Yq-derived long noncoding RNA, Pirmy, which shows unprecedented number of splice variants in testis. Further, Pirmy transcript variants act as templates for several piRNAs. We identified ten differentially expressed autosome-encoded sperm proteins in mutant mice. Pirmy transcript variants have homology to 5/3UTRs of these deregulated autosomal genes. Thus, subfertility in Y-deleted mice appears to be a polygenic phenomenon that is partially regulated epistatically by the Y-chromosome. Our study provides novel insights into possible role of MSY-derived ncRNAs in male fertility and reproduction. Finally, sperm phenotypes from the Y-deleted mice seem to be similar to that reported in inter-specific male-sterile hybrids. Taken together, this study provides novel insights into possible role of Y-derived ncRNAs in male sterility and speciation.

genomics↗