Biology subjects

Calvo, B.

Publications and source records attributed to Calvo, B..

2 recordsLinked to original sources

bioRxiv2026

Carbenoxolone disrupts cell migration by inhibiting the SERCA pump

Collective cell migration is a fundamental process driving tissue repair, angiogenesis, and vascular homeostasis. This coordinated movement requires both intercellular communication via gap junctions and precise intracellular Ca{superscript 2} signaling, largely regulated by the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA) pump within the endoplasmic reticulum (ER). Historically, carbenoxolone (CBX)--a synthetic derivative of glycyrrhetinic acid--has been widely utilized as a pharmacological tool to inhibit gap junctions and dissect their role in collective cell motility. However, its molecular specificity remains highly controversial. In the present study, using different cellular models, we found that CBX drastically reduces collective cell migration by a previously undescribed function for CBX: a fast, potent, and reversible inhibition of the SERCA pump, which provokes a passive leak of the luminal ER Ca{superscript 2} store. Our findings suggest that the effect of CBX over many cellular responses including cell migration and communication, previously only attributed to gap junction blockade, are indeed the consequence of the disruption of intracellular Ca{superscript 2} homeostasis. One Sentence Summarycarbenoxolone blocks cell migration by inhibiting SERCA

physiology↗

bioRxiv2023

Direct measurements of luminal Ca2+ with endo-lysosomal GFP-aequorin (ELGA) reveal functional IP3 receptors

Endo-lysosomes are considered acidic Ca2+ stores but direct measurements of luminal Ca2+ within them are limited. Here we report that the Ca2+-sensitive luminescent protein aequorin does not reconstitute with its cofactor at highly acidic pH but that a significant fraction of the probe is functional within a mildly acidic compartment when targeted to the endo-lysosomal system. We leveraged this probe (ELGA) to report Ca2+ dynamics in this compartment. We show that Ca2+ uptake is ATP-dependent and sensitive to blockers of endoplasmic reticulum Ca2+ pumps. We find that the Ca2+ mobilizing messenger IP3 which typically targets the endoplasmic reticulum evokes robust luminal responses in wild type cells, but not in IP3 receptor knock-out cells. Responses were comparable to those evoked by activation of the endo-lysosomal ion channel TRPML1. Stimulation with IP3-forming agonists also mobilized the store in intact cells. Super-resolution microscopy analysis confirmed the presence of IP3 receptors within the endo-lysosomal system, both in live and fixed cells. Our data reveal a physiologically-relevant, IP3-sensitive store of Ca2+ within the endo-lysosomal system.

physiology↗