Biology subjects

Vega-Lugo, J.

Publications and source records attributed to Vega-Lugo, J..

3 recordsLinked to original sources

bioRxiv2025

Integrins and tetraspanins mediate CD36-actin coupling and regulate CD36 organization and signaling

The actin cortex plays a large role in regulating the dynamic organization of cell surface receptors, which in turn regulates their signaling. However, many receptors have short intracellular domains and no known link to cortical actin. In this work, we identified the {beta}1-integrin subunit and several tetraspanins - CD9, CD81 and CD151 - as part of the hitherto unknown molecular link between the surface receptor CD36 and cortical actin. We found that CD36 in vascular endothelial cells is recruited into complexes/nanodomains containing these proteins, with stronger recruitment near the cell edge. Perturbing this recruitment via the mutation G12V in the N-terminal transmembrane domain of CD36 alters the dynamic organization of CD36 on the vascular endothelial cell surface and weakens its coupling to cortical actin dynamics. Moreover, perturbing this recruitment abolishes thrombospondin-1-induced CD36 signaling through the Src family kinase Fyn. Given their many interactions with other transmembrane proteins, tetraspanins and integrins may provide a ubiquitous mechanism for plasma membrane-cortical actin coupling.

cell biology↗

bioRxiv2022

Confinement of unliganded EGFR by tetraspanin nanodomains gates EGFR ligand binding and signaling

The epidermal growth factor receptor (EGFR) is a central regulator of cell physiology. EGFR is activated by ligand binding, triggering receptor dimerization, activation of kinase activity, and intracellular signaling. EGFR is transiently confined within various plasma membrane nanodomains, yet how this may contribute to regulation of EGFR ligand binding is poorly understood. To resolve how EGFR nanoscale compartmentalization gates ligand binding, we developed single-particle tracking methods to track the mobility of ligand-bound and total EGFR, in combination with modeling of EGFR ligand binding. In comparison to unliganded EGFR, ligand-bound EGFR was more confined and distinctly regulated by clathrin and tetraspanin nanodomains. Ligand binding to unliganded EGFR occurred preferentially in tetraspanin nanodomains, and disruption of tetraspanin nanodomains impaired EGFR ligand binding and altered the conformation of the receptors ectodomain. We thus reveal a novel mechanism by which EGFR confinement within tetraspanin nanodomains regulates receptor signaling at the level of ligand binding.

cell biology↗

bioRxiv2021

Analysis of conditional colocalization relationships and hierarchies from three-color microscopy images

Colocalization analysis of multicolor microscopy images is a cornerstone approach in cell biology. It provides information on the localization of molecules within various subcellular compartments and allows the interrogation of molecular interactions in their cellular context. However, almost all colocalization analyses are designed for two-color images. This limits their applicability and the type of information that they reveal, leading to underutilization of multicolor microscopy images. Here we describe an approach, termed "conditional colocalization analysis," for analyzing the colocalization relationships between three molecular entities in three-color microscopy images. Going beyond the question of whether colocalization is present or not, it addresses the question of whether the colocalization between two entities is influenced, positively or negatively, by their colocalization with a third entity. We showcase two applications of conditional colocalization analysis, one addressing the question of compartmentalization of molecular interactions, and one investigating the hierarchy of molecular interactions in a multimolecular complex. The software for conditional colocalization analysis is available at https://github.com/kjaqaman/conditionalColoc.

cell biology↗