Biology subjects

Tebar, F.

Publications and source records attributed to Tebar, F..

3 recordsLinked to original sources

bioRxiv2025

Fasting-induced hepatic gluconeogenesis is compromised in Anxa6-/- mice

Maintaining constant blood glucose levels is essential for energizing glucose-dependent tissues. During the fed state, insulin lowers elevated blood glucose, while in the fasted state, glucagon maintains blood glucose levels through hepatic stimulation of fatty acid oxidation, glycogenolysis, and gluconeogenesis (GNG). The liver plays a crucial role in these metabolic adaptations. Deregulation of GNG is a hallmark of type 2 diabetes mellitus (T2DM), driven by hepatic insulin resistance, elevated glucagon levels, and excess circulating free fatty acids. Despite normal insulin-sensitive control of glucose levels and effective glycogen mobilization, Anxa6 knockout (Anxa6-/-) mice display rapid hypoglycaemia during fasting. This metabolic disarrangement, in particular during the early stages of fasting is characterized by a low respiratory exchange ratio (RER) and increased lipid oxidation during the diurnal period, indicating a reliance on lipid oxidation due to hypoglycaemia. Elevated glucagon levels during fasting suggest deficiencies in GNG. Further analysis reveals that Anxa6-/- mice are unable to utilize alanine for hepatic GNG, highlighting a specific impairment in the glucose-alanine cycle in fasted Anxa6-/- mice, underscoring the critical role of ANXA6 in maintaining glucose homeostasis under metabolic stress. During fasting, slightly reduced expression levels of alanine aminotransferase 2 (Gpt2) and lactate dehydrogenase (Ldha2), enzymes converting alanine to pyruvate, and the hepatic alanine transporter SNAT4 might contribute to these observations in the Anxa6-/- mice. These findings identify that ANXA6 deficiency causes an inability to maintain glycolytic metabolism under fasting conditions due to impaired alanine-dependent GNG.

physiology↗

bioRxiv2025

Competing signaling pathways controls electrotaxis

Understanding how cells migrate following exogenous cues is one of the most fundamental questions for biology, medicine, and bioengineering. Growing evidence shows that electrotaxis, the directed cell migration toward electric potential gradients, represents a precise and programmable method to control cell migration. Most data suggest that the polarization of membrane components and the following downstream signaling are central to electrotaxis. Unfortunately, how these multiple mechanisms coordinate with the motile machinery of the cell to respond to an electric field is still poorly understood. Here, we develop a mechanistic model that explains and recapitulate electrotaxis across different cell types. Using the zebrafish proteome, we identify membrane proteins directly related to migration signaling pathways that polarize anodally and cathodally. Further, we show that simultaneous and asymmetric distribution of charged membrane receptors towards the anode and the cathode establishes multiple cooperative and competing stimuli for downstream signaling pathways. The resulting polarization of signals controls the actomyosin network dynamics, directing the anodal and cathodal migration of the cell. Our theoretical framework rationalizes the physical processes that determine electrotaxis across cell types and provides a physical framework to test multiple electrotactic pathways. These results together show us how to control cell migration to, e.g., enhance, cancel, or switch directed cell migration, which opens up new avenues not only to promote tissue regeneration or arrest tumor progression but also to design better biomimetic-engineered tissue constructs.

biophysics↗

bioRxiv2021

A mechanosensing mechanism mediated by IRSp53 controls plasma membrane shape homeostasis at the nanoscale

As cells migrate and experience forces from their surroundings, they constantly undergo mechanical deformations which reshape their plasma membrane (PM). To maintain homeostasis, cells need to detect and restore such changes, not only in terms of overall PM area and tension as previously described, but also in terms of local, nano-scale topography. Here we describe a novel phenomenon, by which cells sense and restore mechanically induced PM nano-scale deformations. We show that cell stretch and subsequent compression reshape the PM in a way that generates local membrane evaginations in the 100 nm scale. These evaginations are recognized by the I-BAR protein IRSp53, which triggers a burst of actin polymerization mediated by Rac1 and Arp2/3. The actin polymerization burst subsequently re-flattens the evagination, completing the mechanochemical feedback loop. Our results demonstrate a new mechanosensing mechanism for PM shape homeostasis, with potential applicability in different physiological scenarios. TeaserCell stretch cycles generate PM evaginations of {approx}100 nm which are sensed by IRSp53, triggering a local event of actin polymerization that flattens and recovers PM shape.

biophysics↗