Biology subjects

Majee, A.

Publications and source records attributed to Majee, A..

5 recordsLinked to original sources

bioRxiv2026

Enzyme Activation of Triggerable Polymeric Lysosome Targeting Chimeras

Targeted protein degradation (TPD) has been highly effective for intracellular targets, but extending this approach to extracellular and membrane-bound proteins remains difficult because most extracellular TPD (eTPD) strategies depend on ligand-targeting receptors (LTRs) whose expression and recycling vary across tissues. Existing LTR-independent, multivalent platforms expand the scope of eTPDs by eliminating this dependence on LTRs and enabling cancer-selective designs. Layering in an additional degree of selectivity through endogenously activatable triggers, such as overexpressed enzymes, can enhance the tissue tropism of the LTR-independent platforms and widen therapeutic window. Here we report triggerable polymeric lysosome targeting chimeras (tPolyTACs), which combine antibody-defined targeting with locally triggered covalent capture. tPolyTACs conjugate monoclonal antibodies to phosphatase-cleavable substrates that, upon engagement of endogenous cell-surface phosphatases, unmask a reactive quinone methide electrophile, covalently trapping the target complex and driving its clathrin-mediated internalization and autolysosomal degradation. We show tPolyTAC-mediated degradation of the membrane proteins EGFR, PD-L1, and cMET, and demonstrate that para-substituted electrophiles outperform ortho-substituted analogues likely due to more favorable active-site positioning. These results establish tPolyTACs as a modular, covalent, enzyme-responsive platform that resolves the efficiency-selectivity trade-off limitations in extracellular degradation.

cell biology↗

bioRxiv2026

Repulsion-Driven Layering in Polymer-Assisted Condensation

The hierarchical organization of multiphase biomolecular condensates into core-shell architectures is a fundamental problem in soft matter and biophysics. While classical explanations rely on hierarchies of interfacial tension ({gamma}) between coexisting liquids, the ultralow tensions of condensates (0.1-1 {micro}N/m) render such hierarchies potentially fragile. We introduce a robust assembly principle based on Polymer-Assisted Condensation (PAC), in which a single polymer species dictates the entire structure. The polymer nucleates a dense core by recruiting a condensation-incompetent protein (P1). A second incompetent protein (P2), which is repelled or otherwise thermodynamically disfavored from entering the polymer-rich core, is nonetheless recruited to the interface by weak attraction to P1, forming a stable shell. This effective repulsion-driven layering operates across a wide parameter space without requiring{gamma} asymmetries and yields a robust structure that is impervious to concentration fluctuations and environmental perturbations. Phase-field modeling and molecular simulations establish this mechanism and capture key features of nucleolar organization. Our work reveals a general physical pathway for encoding spatial order in soft, multicomponent fluids.

biophysics↗

bioRxiv2025

Antagonistic and Synergistic Roles of Tomato AFP3 Isoforms in Hormonal Regulation and Development

The ABA INSENSITIVE5 BINDING PROTEIN (AFP) family plays a critical role in abscisic acid (ABA) signaling through interaction with the transcription factor ABI5, impacting seed germination and stress responses. Here, we characterize tomato AFP3, which produces two isoforms: a full-length protein and a shorter microProtein (sAFP3) containing only the C-terminal domain. Functional analyses reveal contrasting roles of these isoforms in development; while AFP3 overexpression accelerates shoot growth but impairs seed germination, both afp3 loss-of-function and sAFP3-expressing mutants (afp3-D) exhibit stunted growth and developmental defects. Transcriptome profiling highlights that AFP3 and sAFP3 differentially regulate hormone-related pathways, including salicylic acid, gibberellic acid, and jasmonic acid metabolism. Proteomic interaction studies demonstrate that AFP3 and sAFP3 physically interact, sharing partners involved in hormone signaling. Hormone quantification confirms that AFP3 modulates multiple phytohormones, with elevated ABA in afp3-D mutants and increased gibberellic acid, jasmonic acid, and salicylic acid in both afp3 and afp3-D mutant backgrounds. Moreover, AFP3 controls flower and fruit development, influencing yield and ripening. Together, these findings identify AFP3 as a key integrator of hormonal crosstalk that coordinates growth, development, and stress responses in tomato. The production of dual AFP3 isoforms through alternative transcription, combined with microProtein-mediated dominant-negative regulation, reveals a sophisticated mechanism for dynamically fine-tuning transcriptional networks. This versatile strategy underscores how plants--and potentially other organisms--achieve precise control over complex signaling pathways.

plant biology↗

bioRxiv2025

Polymer-assisted condensation as key to chromatin localization

We put forward a novel mechanism to account for the experimentally observed positional shifts of chromosomes within the cell nucleus, which appear to be driven by compositional alterations in the nuclear lamina [Science 7, eabf6251 (2021)]. By considering chromatin as a biomolecular condensate we demonstrate that the adsorption of the chromatin-binding proteins at the lamina leads to a wetting of the condensate while spreading of the chromatin on the lamina is avoided. This leads to the non-monotonous density profile of the polymer with respect to the surface which can be explained by the competition between the tendency of the protein component to wet the surface and the conformational restrictions of the polymer near the impenetrable surface. A change in the composition of the lamina can lead to repositioning of chromatin towards the center of the nucleus. We explore various mechanisms by which lamina compositional shifts could lead to the dewetting of the condensate. Our theory not only offers an explanation for specific chromatin conformation experiments, but also contributes to the broader understanding of wetting onto responsive surfaces in multi-component systems.

biophysics↗

bioRxiv2025

SlHSFB3a developmentally regulates lateral root formation by modulating auxin signaling in tomato.

O_LIThe function of HSFs, known otherwise as master thermoregulators, in plant developmental remains largely uninvestigated. C_LIO_LIIn this study, we strategically analyze SlHSFB3a, a class B sub member of HSF transcription factor family, uniquely expresses in age-dependent tomato roots and improves root architecture by synchronizing auxin homeostasis. C_LIO_LIThis data demonstrates SlHSFB3a overexpressed transgenics display higher lateral root (LR) density and early LR emergence improving root architecture. Generation of CRISPR-Knockout mutants displayed contrasting phenotype, confirming SlHSFB3as vital role in root growth. In SlHSFB3a manipulated roots, concentration gradient auxin responses oscillated with increase in LR number. C_LIO_LIWe highlight the signal transduction of SlHSFB3a mediated auxin activation that enhances tomato LRs. SlHSFB3a directly inhibits auxin repressors, increases auxin flow via ARF7/LOB20 pathway and positively modulates LR growth. C_LI

plant biology↗