Biology subjects

Lavoie, C.

Publications and source records attributed to Lavoie, C..

3 recordsLinked to original sources

bioRxiv2026

SNX2, but not SNX1, regulates the hepatocyte growth factor receptor MET in HCT116 colorectal cancer cells

Aberrant signaling of receptor tyrosine kinases (RTKs), including the hepatocyte growth factor receptor MET, contributes to colorectal cancer (CRC) progression and is tightly regulated by endocytic trafficking. We previously showed that combined deletion of the endosomal sorting proteins SNX1 and SNX2 disrupts MET trafficking and enhances downstream signaling in HCT116 CRC cells. However, their individual contributions remained unresolved. Using CRISPR/Cas9-engineered SNX1- and SNX2-KO HCT116 cells, we examined their roles in MET trafficking and signaling. Loss of SNX2, but not SNX1, markedly reduced SNX5 and SNX6 protein levels without affecting transcript abundance. SNX2 deficiency also increased total MET under serum-containing conditions without altering MET transcript or cell-surface receptor levels. Following HGF stimulation, loss of SNX2, but not SNX1, transiently delayed MET trafficking to EEA1+ early and RAB7+ late endosomes, while recycling and lysosomal trafficking remained largely unaffected. This was accompanied by enhanced and sustained HGF-induced AKT activation. Together, these findings identify SNX2 as a predominant regulator of early MET endosomal trafficking in HCT116 cells and reveal functional asymmetry between SNX1 and SNX2. They support a role for SNX2 in spatial regulation of MET signaling through receptor trafficking, consistent with the association of low SNX2 expression with poorer survival in CRC patients.

cell biology↗

bioRxiv2025

Evolutionary and ontogenetic shifts from aquatic to terrestrial light environments in frogs provide new insights into the vertebrate phototransduction cascade

Evolutionary studies of vertebrate vision have mainly focused on the light-sensitive opsins neglecting the downstream phototransduction cascade. Here, we investigate patterns of gene loss and expression across jawed vertebrates, providing clarity on the evolution of phototransduction. We next focus on an ecologically diverse sample of frogs represented by whole-eye transcriptomes and genomes from 113 species. We tested the hypothesis that phototransduction genes were lost in the common ancestor of frogs due to nocturnality and that functional differences in phototransduction are driven by variation in habitat, activity pattern, and life history. Across frogs, we recovered 38 of 39 vertebrate phototransduction genes, with all but one of these (GUCA1B2) consistently expressed in frog eyes. This contrasts the high level of gene loss found in other ancestrally nocturnal tetrapods (e.g., mammals and snakes) and is more similar to ray-finned fishes. More than other ecological traits, we found that loss of the larval aquatic life stage (direct development) and inhabiting aquatic and semiaquatic habitats as adults were most strongly associated with shifts in selective strength, with widespread signals of both positive and relaxed selection across frog phototransduction genes. These findings suggest that phototransduction is under different functional constraints in aquatic versus terrestrial light environments and that shifts in the use of these environments have played a strong role in frog visual evolution. Collectively, these results reinforce that frogs are of particular interest for vertebrate visual evolution because they span both an evolutionary and an ontogenetic transition from vision underwater to vision on land.

evolutionary biology↗

bioRxiv2025

Isoform-Dependent Loss- and Gain-of-Function of the Gαs K53N Variant in Human Disease

The K53N mutation in Gs has been identified in patients with Albrights Hereditary Osteodystrophy (AHO), pseudohypoparathyroidism type 1A (PHP1a), and dilated cardiomyopathy; however, its molecular mechanism remains unclear. Here, we characterize the molecular, cellular, and physiological consequences of the K53N mutation in both long and short isoform of Gs. Biochemical analyses reveal that K53N disrupts nucleotide exchange and GTP hydrolysis, rendering both the short (Gs-S) and long (Gs-L) isoforms unresponsive to activation by G protein-coupled receptors (GPCRs) or cholera toxin. Both isoforms display a loss-of-function phenotype, failing to trigger cAMP production in response to {beta}2-adrenergic, parathyroid hormone, or vasopressin receptor stimulation. Notably, only the long isoform (Gs-L K53N) displays constitutive, receptor-independent cAMP generation. The mutation also reduces protein stability, weakens G{beta}{gamma} subunit interaction, and reduces plasma membrane localization. In neonatal rat ventricular cardiomyocytes, K53N impairs cAMP signaling and exerts dominant-negative effects on isoproterenol-induced responses. Strikingly, only Gs-L K53N abolishes isoproterenol-stimulated calcium release, directly implicating this isoform in the pathogenesis of cardiomyopathy. Collectively, these findings identify K53N as a unique Gs mutation that confers both loss- and gain-of-function properties in an isoform-specific manner, providing mechanistic insight into its complex pathogenicity in endocrine and cardiac tissues.

pharmacology and toxicology↗