Biomedical subjects

Graciela A Borioli

Publications and source records attributed to Graciela A Borioli.

6 recordsLinked to original sources

PubMed2006

Surface thermodynamics reveals selective structural information storage capacity of c-Fos-phospholipid interactions.

The surface properties of c-Fos, a regulator of normal and pathologic cell growth and a modulator of phospholipid metabolism, suggest that it has the potential to transduce information through molecular reorganization, placing the nature of its interaction with phospholipids at the basis of its possible effects at the membrane level. Previous studies established that c-Fos induces condensation and depolarization of PIP2 films and expansion and hyperpolarization of PC. We have now explored more in depth the thermodynamic aspects of these lipid-protein interactions, finding that the mixtures have associated hysteresis. The analysis of the excess thermodynamic functions provides evidence of entropic-enthalpic compensations that result in a favorable enthalpic contribution derived from the interaction of c-Fos with PIP2, which exceeds the unfavorable configurational entropy. On the contrary, favorable entropy terms dominate the interaction of c-Fos with PC over the unfavorable enthalpy. The free energy of hysteresis is stored as excess free energy. A shift in molecular packing-dependent surface reorganization, compared to that of ideally mixed films, indicates a gain in information content at the lipid-protein interface in mixed films of c-Fos with PIP2 but not with PC. It is postulated that the free energy stored in these mixtures could act as a bidirectional structural information transducer for dynamic compression-expansion processes occurring on the membrane surface.

Animals↗

PubMed2005

c-Jun interacts with phospholipids and c-Fos at the interface.

We describe c-Jun, a widely studied transcription factor that participates in cell proliferation, differentiation, and tumorigenesis, as amphitropic. We show that c-Jun forms stable monolayers and interacts favorably, although in a nonselective manner, with phospholipids at the interface. The surface activity of c-Jun, together with that of c-Fos, its common partner in AP-1 transcription heterodimers, drives interfacial complex formation. We show that AP-1 is very stable at the air-water interface and suggest that AP-1 may not be substantially formed in solution as a stable equimolar association of both proteins.

Binding, Competitive↗

PubMed2005

c-Fos and phosphatidylinositol-4,5-bisphosphate reciprocally reorganize in mixed monolayers.

The transcription factor c-Fos has surface thermodynamic properties that allow it to differentially interact with phospholipids, especially PIP2. It regulates phospholipid metabolism both in vivo and in vitro, and modulates degradation of phospholipid monolayers by phospholipases in a way that depends on the membrane intermolecular packing (i.e., surface lateral pressure). With the aim to understand details of the interactions of c-Fos at the membrane level, we studied the surface packing, dipole potential, compressibility and topography of mixed films of the protein with PIP2. We show that c-Fos changes the packing of liquid-expanded PIP2 monolayers, in a different manner with respect to its effect on the similarly liquid-expanded dilauroylphosphatidylcholine monolayers. The changes at the local molecular level are transduced to long-range inhomogeneities of the surface, detected by Brewster angle (BAM) and epifluorescence microscopy (EFM). Our results highlight the capacity of c-Fos to alter the packing and dipole potential of the lipid-protein interface. This involves variations of the surface in-plane elasticity and lateral segregation of phase domains. These dynamic, reversible alterations of surface organization provide a basis by which c-Fos may transduce molecular information at the membrane level.

Membranes, Artificial↗

PubMed2004

Phospholipase activity is modulated by c-Fos through substrate expansion and hyperpolarization.

c-Fos, a component of AP-1 transcription factors, has been shown to have marked amphitropic properties and to regulate phospholipase activity against lipid monolayers. In agreement with its high surface activity, it has also been found to associate to membranes of the endoplasmic reticulum and to activate phospholipid metabolism in vivo. All these findings point to an involvement of this oncoprotein within a membrane environment. We have previously shown that c-Fos modulates in different manners the activity of phospholipase A2 and phospholipase C against monolayers of dilauroylphosphatidylcholine (PC). In this work, we have studied the possible molecular mechanism underlying the phosphohydrolytic modulation. Our results show that c-Fos expands and hyperpolarizes PC, indicating that its effects on these enzymatic activities are due to the changes it induces on the interfacial organization of the substrate.

Animals↗

PubMed2004

c-Fos activated phospholipid synthesis is required for neurite elongation in differentiating PC12 cells.

We have previously shown that c-Fos activates phospholipid synthesis through a mechanism independent of its genomic AP-1 activity. Herein, using PC12 cells induced to differentiate by nerve growth factor, the genomic effect of c-Fos in initiating neurite outgrowth is shown as distinct from its nongenomic effect of activating phospholipid synthesis and sustaining neurite elongation. Blocking c-Fos expression inhibited differentiation, phospholipid synthesis activation, and neuritogenesis. In cells primed to grow, blocking c-Fos expression determined neurite retraction. However, transfected cells expressing c-Fos or c-Fos deletion mutants with capacity to activate phospholipid synthesis sustain neurite outgrowth and elongation in the absence of nerve growth factor. Results disclose a dual function of c-Fos: it first releases the genomic program for differentiation and then associates to the endoplasmic reticulum and activates phospholipid synthesis. Because phospholipids are key membrane components, we hypothesize this latter phenomenon as crucial to support membrane genesis demands required for cell growth and neurite elongation.

Animals↗

PubMed2002

c-Fos is a surface pressure-dependent diverter of phospholipase activity.

c-Fos, a transcription factor, associates to endoplasmic reticulum and modulates phospholipid biosynthesis. Its surface thermodynamic properties allow it to differentially interact with phospholipid monolayers with a selective dependence on the lipid polar head group and the lateral surface pressure. We explored the c-Fos ability to modulate phospholipid degradation by phospholipases (ppPLA2, Bacillus cereus PLC, and sphingomyelinase) using the monolayer technique. Experiments conducted under constant packing conditions show that c-Fos modulates phospholipase activity in a finely tuned way, depending on the membrane intermolecular packing. Surface lateral pressures above 12-16 mN/m induce c-Fos to activate phospholipase A2 and sphingomyelinase, and abolish phospholipase C activity. The effects of c-Fos on other steps of the catalytic process, lag-time and extent, are synergic with those on activity. We show for the first time that c-Fos participates in modulating phospholipid degradation and that it can affect the formation of lipid second messenger products by PLA2, PLC, and sphingomyelinase.

Animals↗