Biology subjects

Gelova, Z.

Publications and source records attributed to Gelova, Z..

3 recordsLinked to original sources

bioRxiv2024

The solute carrier superfamily interactome

Solute carrier (SLC) transporters form a protein superfamily that enables transmembrane transport of diverse substrates including nutrients, ions and drugs. There are about 450 different SLCs, residing in a variety of subcellular membranes. Loss-of-function of an unusually high proportion of SLC transporters is genetically associated with a plethora of human diseases, making SLCs a rapidly emerging but challenging drug target class. Knowledge of their protein environment may elucidate the molecular basis for their functional integration with metabolic and cellular pathways and help conceive pharmacological interventions based on modulating proteostatic regulation. We aimed at obtaining a global survey of the SLC protein interaction landscape and mapped the protein-protein interactions of 396 SLCs by interaction proteomics. We employed a functional assessment based on RNA interference of interactors in combination with measurement of protein stability and localization. As an example, we detail the role of a SLC16A6 phospho-degron, and the contributions of PDZ-domain proteins LIN7C and MPP1 to the trafficking of SLC43A2. Overall, our work offers a resource for SLC-protein interactions for the scientific community.

systems biology↗

bioRxiv2022

Cell surface auxin signalling directly targets PIN-mediated auxin fluxes for adaptiveplant development

Phytohormone auxin and its directional transport mediate much of the remarkably plastic development of higher plants. Positive feedback between auxin signaling and transport is a key prerequisite for (i) self-organizing processes including vascular tissue formation and (ii) directional growth responses such as gravitropism. Here we identify a mechanism, by which auxin signaling directly targets PIN auxin transporters. Via the cell-surface ABP1-TMK1 receptor module, auxin rapidly induces phosphorylation and thus stabilization of PIN2. Following gravistimulation, initial auxin asymmetry activates autophosphorylation of the TMK1 kinase. This induces TMK1 interaction with and phosphorylation of PIN2, stabilizing PIN2 at the lower root side, thus reinforcing asymmetric auxin flow for root bending. Upstream of TMK1 in this regulation, ABP1 acts redundantly with the root-expressed ABP1-LIKE auxin receptor ABL3. Such positive feedback between cell-surface auxin signaling and PIN-mediated polar auxin transport is fundamental for robust root gravitropism and presumably also for other self-organizing developmental phenomena.

plant biology↗

bioRxiv2019

Cell-surface receptors enable perception of extracellular cytokinins

Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience 1,2. Although cytokinin receptors are substantially localised to the endoplasmic reticulum 3-5, the cellular sites of cytokinin perception continue to be debated 1,6,7. Several cytokinin types display bioactivity 8,9 and recently a cell-specific cytokinin gradient was reported in roots 10. Yet, the importance of spatially heterogeneous cytokinin distribution and the specific cytokinin(s) that account for the different responses remain unclear. Here we show that cytokinin perception by plasma membrane receptors is an effective path for cytokinin response in root cells. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP;11) is closely matched to intracellular cytokinin content, yet a proportion of bioactive cytokinins are detected in the extracellular fluid. Using cytokinins covalently linked to beads that could not pass the plasma membrane, we demonstrate that strong TCSn activation still occurs and that this response is greatly diminished in cytokinin receptor mutants. Although intracellular receptors play significant roles, we argue for a revision of concepts of cytokinin perception to include the spatial dimensions. In particular, selective ligand-receptor affinities, cellular localisation and tissue distribution of bioactive cytokinins, their receptors, transporters and inactivation enzymes appear all to be components of the signalling regulatory mechanisms.

plant biology↗