Biology subjects

Mayorga, L. S.

Publications and source records attributed to Mayorga, L. S..

3 recordsLinked to original sources

bioRxiv2025

Unconventional Fusion Mechanism at the Origin of Eukaryotic Membranes

Eukaryogenesis remains one of biologys most intriguing transitions, yet the events driving the emergence of the eukaryotic cell membrane have not been sufficiently explored. Canonical membrane fusion models, are not appropriate to explain the transition from an archaeal cell membrane to a bacterial one, via heterochiral intermediates. Here, we show that a non-canonical, lipid-mediated mechanism spontaneously generates closed bilayers of mixed bacterial and archaeal lipids. Using as a proxy a combination of enhanced-sampling and unbiased molecular dynamics simulations, we demonstrate that transient edge-mediated archaeal intermediates merge with bacterial vesicles without the formation or expansion of a fusion pore. Key indicators include reduced energy barriers and significant membrane stability post-fusion. The edge-induced route bridges the inconsistencies found in protocell models and protein-dependent pathways, proposing an unconventional explanation that describes how early eukaryotic systems achieved membrane continuity. These findings provide a plausible biophysical basis for the origin of the eukaryotic plasma membrane.

biophysics↗

bioRxiv2022

The molecular chaperone Cysteine String Protein is required to stabilize trans-SNARE complexes during human sperm acrosomal exocytosis

Membrane fusion in sperm cells is crucial for acrosomal exocytosis and must be preserved to assure fertilizing capacity. Evolutionarily conserved protein machinery regulates acrosomal exocytosis. Molecular chaperones play a vital role in spermatogenesis and post-testicular maturation. Cysteine String Protein (CSP) is a member of the Hsp40 co-chaperones, and for more than 20 years, most research published focused on CSPs role in synapsis. However, the participation of molecular chaperones in acrosomal exocytosis is poorly understood. Using western blot and indirect immunofluorescence, we showed that CSP is present in human sperm, is predominantly bound to membranes, and is palmitoylated. Moreover, using electron microscopy and functional assays, we reported that sequestration of CSP avoided the assembly of trans-complexes and inhibited exocytosis. In summary, our data demonstrated that CSP is necessary and mediates the trans-SNARE complex assembly between the outer acrosomal and plasma membranes, thereby regulating human sperm acrosomal exocytosis. Understanding CSPs role is critical in identifying new biomarkers and generating new rational-based approaches to treating male infertility. Summary statementCysteine String Protein is necessary and mediates the trans-SNARE complex assembly between the outer acrosomal and plasma membranes, thereby regulating human sperm acrosomal exocytosis.

cell biology↗

bioRxiv2020

From cartoons to quantitative models in Golgi transport

Cell biology is evolving to become a more formal and quantitative science. In particular, several mathematical models have been proposed to address Golgi self-organization and protein and lipid transport. However, most scientific articles about the Golgi apparatus are still using static cartoons to represent their findings that miss the dynamism of this organelle. In this report, we show that schematic drawings of Golgi trafficking can be easily translated into an Agent-Based Model (ABM) using the Repast platform. The simulations generate an active interplay among cisternae and vesicles rendering quantitative predictions about Golgi stability and transport of soluble and membrane-associated cargoes. The models can incorporate complex networks of molecular interactions and chemical reactions by association with COPASI, a software that handles Ordinary Differential Equations. The strategy described provides a simple, flexible, and multiscale support to analyze Golgi transport. The simulations can be used to address issues directly linked to the mechanism of transport or as a way to incorporate the complexity of trafficking to other cellular processes that occur in dynamic organelles.

cell biology↗