Biology subjects

Abhinav, K.

Publications and source records attributed to Abhinav, K..

3 recordsLinked to original sources

bioRxiv2022

Shared and distinctive neighborhoods of emerin and LBR revealed by proximity labeling and quantitative proteomics

Emerin and LBR are abundant transmembrane proteins of the nuclear envelope (NE) that are concentrated at the inner nuclear membrane (INM). Although both proteins interact with chromatin and nuclear lamins, they have distinctive biochemical and functional properties. Here we have deployed proximity labeling using the engineered biotin ligase TurboID (TbID) and quantitative proteomics to compare the neighborhoods of emerin and LBR in cultured mouse embryonic fibroblasts (MEFs). Our analysis revealed 232 high confidence proximity partners (HCPP) that interact selectively with emerin and/or LBR, 49 of which are shared by both. These included previously characterized NE-concentrated proteins, as well as a host of additional proteins not previously linked to emerin or LBR functions. Many of these are TM proteins of the ER and include two E3 ubiquitin ligases. Using the proximity ligation assay as an orthogonal approach, we validated the interactions described by proximity labeling for 11/12 proteins analyzed, supporting the robustness of our analysis. Overall, this work presents methodology that may be used for large-scale mapping of the landscape of the INM and reveals a group of new proteins with potential functional connections to emerin and LBR.

cell biology↗

bioRxiv2019

The conserved metalloprotease invadolysin is present in invertebrate haemolymph and vertebrate blood

We identified invadolysin, a novel essential metalloprotease, for functions in chromosome structure, cell proliferation and migration. Invadolysin also plays an important metabolic role in insulin signaling and is the only protease known to localise to lipid droplets, the main lipid storage organelle in the cell. In silico examination of the protein sequence of invadolysin predicts not only protease and lipase catalytic motifs, but also post-translational modifications and the secretion of invadolysin. Here we show that the protease motif of invadolysin is important for its role in lipid accumulation, but not in glycogen accumulation. The lipase motif does not appear to be functionally important for accumulation of lipids or glycogen. Post-translational modifications likely contribute to modulating the level, localisation or activity of invadolysin. We identified a secreted form of invadolysin in the soluble fraction of invertebrate hemolymph (where we observe sexually dimorphic forms) and also vertebrate plasma, including in the extracellular vesicle fraction. Biochemical analysis for various post-translational modifications demonstrated that secreted invadolysin is both N-and O-glycosylated, but not apparently GPI-linked. The discovery of invadolysin in the extracellular milieu suggests a role for invadolysin in normal organismal physiology.\n\nSummary StatementIn this study, we show that the conserved metalloprotease invadolysin is present in invertebrate hemolymph and vertebrate blood, suggesting the protein may function in organismal physiology.

cell biology↗

bioRxiv2018

Improved Accuracy of Diffusion MRI Tractography Using Topology-Informed Pruning (TIP)

Diffusion MRI fiber tracking provides a non-invasive method for mapping the trajectories of human brain connections, but its false connection problem has been a major challenge. This study introduces topology-informed pruning (TIP), a method that automatically identifies singular tracts and eliminates them to improve the tracking accuracy. The accuracy of the tractography with and without TIP was evaluated by a team of 6 neuroanatomists in a blinded setting to examine whether TIP could improve the accuracy. The results showed that TIP improved the tracking accuracy by 11.93% in the single-shell scheme and by 3.47% in the grid scheme. The improvement is significantly different from a random pruning (p-value < 0.001). The diagnostic agreement between TIP and neuroanatomists was comparable to the agreement between neuroanatomists. The proposed TIP algorithm can be used to automatically clean up noisy fibers in deterministic tractography, with a potential to confirm the existence of a fiber connection in basic neuroanatomical studies or clinical neurosurgical planning.

neuroscience↗