Copper nanoclusters (CuNCs) exhibit a high tendency to undergo oxidation particularly at the subnanometer size regime. In the light of overcoming this bottleneck, we have been successful in developing tripeptide (glutathione, GSH) templated CuNCs which show high biocompatibility and stability, in spite of being ultrafine in size. These blue-emitting CuNCs possess very promising optical features such as significant quantum yield (QY) and excellent photostability. Our cell-imaging studies reveal that the CuNCs localize primarily in nuclear membranes of the different cancerous (Hela, MDAMB-231, and A549) cells, and the cell viability assay conclusively established their nontoxic nature. Apart from their biological significances, these CuNCs also illustrate their ability to serve as a metal ion sensor, selectively detecting Fe 3+ ions in solution at the nanomolar concentration regime. This unique luminescent property of the NCs will enable them to serve as label-free and versatile probes having several biological and analytical applications.

Retromer, a peripheral membrane protein complex, plays an instrumental role in host of cellular processes by its ability to recycle receptors from endosomes to the trans-Golgi network. It consists of two distinct sub-complexes, a membrane recognizing, sorting nexins (SNX) complex and a cargo recognition, vacuolar protein sorting (Vps) complex. Small

The endosomal protein-sorting machineries play vital roles in diverse physiologically important cellular processes. Much of the core membrane-sorting apparatus is conserved in evolution, such as retromer, which is involved in the recycling of a diverse set of cargoes via the retrograde trafficking route. Here, in an RNAi-based loss-of-function study, we identified that suppression of SNX12 leads to a severe blockage in CIM6PR (also known as IGF2R) transport and alters the morphology of the endocytic compartments. We demonstrate that SNX12 is involved in the early phase of CIM6PR transport, and mediates receptor recycling upstream of the other well-established SNX components of retromer. Ultra-structural analysis revealed that SNX12 resides on tubulo-vesicular structures, despite it lacking a BAR domain. Furthermore, we illustrate that SNX12 plays a key role in intraluminal vesicle formation and in the maturation of a subpopulation of early endosomes into late endosomes, thereby regulating selective endocytic transport of cargo for degradation. This study therefore provides evidence for the existence of early endosomal subpopulations that have differential roles in the sorting of the cargoes along endocytic degradative pathways.

We describe a straightforward strategy for the synthesis of strongly fluorescent pyridoindoles by Pd-catalyzed oxidative annulations of internal alkynes with C-3 functionalized indoles through CH/NH bond activation in a one-pot tandem process. Mechanistic investigations reveal the preferential activation of NH indole followed by CH activation during the cyclization process. Photophysical properties of pyridoindoles exhibited the highest fluorescence quantum yield of nearly 80 %, with emission color varying from blue to green to orange depending on the substructures. Quantum mechanical calculations provide insights into the observed photophysical properties. The strong fluorescence of the pyrido[1,2-a]indole derivative has been employed in subcellular imaging, which demonstrates its localization in the cell nucleus.

Sorting nexins (SNX) are a family of proteins containing the Phox homology domain, which shows a preferential endo-membrane association and regulates cargo sorting processes. Here, we established that SNX32, a SNX-BAR (Bin/Amphiphysin/Rvs) sub-family member associates with SNX4 via its BAR domain and the residues A226, Q259, E256, R366 of SNX32, and Y258, S448 of SNX4 that lie at the interface of these two SNX proteins mediates this association. SNX32, via its PX domain, interacts with the Transferrin receptor (TfR) and Cation Independent Mannose-6-Phosphate Receptor (CIMPR), and the conserved F131 in its PX domain is important in stabilizing these interactions. Silencing of SNX32 leads to a defect in intracellular trafficking of TfR and CIMPR. Further, using SILAC-based differential proteomics of the wild type and the mutant SNX32, impaired in cargo binding, we identified Basigin (BSG), an immunoglobulin superfamily member, as a potential interactor of SNX32 in SHSY5Y cells. We then demonstrated that SNX32 binds to BSG through its PX domain and facilitates its trafficking to the cell surface. In Neuro-Glial cell lines, silencing of SNX32 leads to defects in neuronal differentiation. Moreover, abrogation in lactate transport in the SNX32 depleted cells led us to propose that SNX32 may contribute to maintaining the neuro-glial coordination via its role in BSG trafficking and the associated Monocarboxylate transporter activity. Taken together, our study showed that SNX32 mediates the trafficking of specific cargo molecules along distinct pathways.