Biology subjects

Costantini, S.

Publications and source records attributed to Costantini, S..

4 recordsLinked to original sources

bioRxiv2025

Mechanical Cues Regulate Cargo Sorting and Export at the Golgi

The secretory pathway is a sophisticated endomembrane machinery designed to transport and deliver proteins and lipids to intracellular organelles and the extracellular space. While the molecular components of the secretory pathway are well understood, less is known about their regulation, especially by mechanical cues. Here, we report that substrate stiffness stimulates conventional secretion. We have unravelled a molecular pathway that links a mechanical cue through Src and FAK kinases to promote the trafficking of secretory proteins out of the Golgi apparatus and prevent their post-Golgi lysosomal degradation. Phosphoproteomic analysis revealed the Golgi-specific Brefeldin A resistance factor 1 (GBF1) as a key downstream mechano-responsive regulator, whose phosphorylation state orchestrates post-Golgi cargo sorting, directing proteins either toward secretion or to lysosomes. Finally, we identified AMPK as a stiffness-dependent upstream regulator of GBF1 phosphorylation. Together, our data reveal a molecular regulatory loop in which matrix stiffness positively regulates cellular secretion via the Src-FAK-AMPK-GBF1 axis, which can have relevant medical implications in conditions like cancer and fibrosis and their treatment.

cell biology↗

bioRxiv2024

Berberine Bridge enzyme-like oxidases orchestrate homeostatic control and signaling of oligogalacturonides in defense and wounding

Plant immunity is triggered by endogenous elicitors known as damage-associated molecular patterns (DAMPs). Oligogalacturonides (OGs) are DAMPs released from the cell wall (CW) demethylated homogalacturonan during microbial colonization, mechanical or pest-provoked tissue damage, and physiological CW remodeling. Berberine Bridge Enzyme-like (BBE-l) proteins named OG oxidases (OGOXs) have been proposed to govern OGs homeostasis, which is necessary to avoid deleterious growth-affecting hyper-immunity and possible cell death. Using OGOX1 over-expressing lines and ogox1/2 double mutants, we show that these enzymes determine the levels of active OGs vs. inactive oxidized products (oxOGs). The ogox1/2-deficient plants have elevated levels of OGs, while plants overexpressing OGOX1 accumulate oxOGs. The balance between OGs and oxOGs affect disease resistance against Pseudomonas syringae pv tomato, Pectobacterium carotovorum, and Botrytis cinerea depending on the microbial capacity to respond to OGs and metabolize oxOGs. Gene expression upon plant infiltration with OGs reveals that OGOXs orchestrate OG signaling in defense as well as upon tissue damage, pointing to these enzymes as apoplastic players in immunity and tissue repair. TeaserOxidases control the homeostasis of oligogalacturonides in the cell wall and play a pivotal role in the plant immunity.

plant biology↗

bioRxiv2023

BERBERINE BRIDGE ENZYME-LIKE OXIDASES OF CELLODEXTRINS AND MIXED-LINKED β-GLUCANS CONTROL SEED COAT FORMATION

A member of the Arabidopsis Berberine Bridge Enzyme-like (BBE-l) protein family named CELLODEXTRIN OXIDASE 2 (CELLOX2) has been characterized in this paper and shown to display structural and enzymatic features similar to the previously characterized CELLOX1. These include the capability to oxidize the mixed-linked {beta}-1[->]3/{beta}-1[->]4-glucans (MLGs), recently described as cell wall-derived damage-associated molecular patterns (DAMPs) that activate plant immunity. The two paralogous genes show a different expression profile. Unlike CELLOX1, CELLOX2 is not expressed in seedlings or in adult plants and is not involved in immunity against Botrytis cinerea. Both genes are expressed in a concerted manner in the seed coat during development: whereas CELLOX2 transcripts are detected mainly during the heart stage, CELLOX1 transcripts are detected later, when the expression of CELLOX2 decreases. Analysis of seeds of cellox1 and cellox2 knock-out mutants show alterations in the structure of the coat and mucilage, but not in their monosaccharide composition. We propose that the cell wall structure of specific organs is not only the result of a coordinated synthesis/degradation of polysaccharides but also of their exposure to enzymatic oxidation. Our results also reinforce the view that the family of BBE-l proteins is at least in part devoted to the control of the activity of cell wall-derived oligosaccharides acting as DAMPs. SENTENCETwo Arabidopsis BBE-like oxidases of the cell wall DAMPs cellodextrins and mixed-linked {beta}-glucans inactivate their elicitor activity. Seed coat and mucilage are altered in null mutants of two enzymes.

plant biology↗

bioRxiv2018

Interferon-alpha2 but not interferon-gamma serum levels are associated with intramuscular fat in obese patients with nonalcoholic fatty liver disease

BackgroundIntramuscular triglycerides (IMTGs) represent an important energy supply and a dynamic fat-storage depot that can expand during periods of elevated lipid availability and a fatty ac-id source. Ultrasonography (US) of human skeletal muscles is a practical and reproducible method to assess both IMTG presence and entity.\n\nAlthough a crosstalk between cytokines in skeletal muscle and adipose tissue has been suggested in obesity, condition leading to hepatic steatosis (HS) or better defined as nonalcoholic fatty liver disease and cancer, there are still questions to be answered about the role of interferons (IFNs), alpha as well as gamma, and IMTG in obesity. We aimed at discovering any correlation between IFNs and IMTG.\n\nMethodsWe analysed anthropometric data, metabolic parameters and imaging features of a population of obese subjects with low-prevalence of co-morbidities but HS. The levels of serum IFNs were detected by a magnetic bead-based multiplex immunoassays.\n\nResultsSerum concentrations of IFN-alpha2 were increased, while serum levels of IFN-gamma were decreased confronted with those of controls; the severity of IMTG, revealed at US as Heckmatt scores, was inversely predicted by IFN-alpha2 serum concentrations; IMTG scores were not predicted by serum levels of IFN-gamma; IMTG scores were predicted by HS severity, ascertained at US; HS severity was predicted by visceral adipose tissue, assessed by US, but the latter was not instrumental to IMTG.\n\nDiscussion & ConclusionThis study has added some pieces of observation about the cytokine network regulating the interplay between IMTG and obesity in obese patients with HS.

epidemiology↗