Abstract
BackgroundThe signalling cascades involved in many biological processes require the coordination of different subcellular districts. It is the case of the pathways involved in spermatozoa acquisition of fertilizing ability (the so called "capacitation"). In the present work the coordination of subcellular signalling, during the boar sperm capacitation, was studied by a computational and experimental approach. As first the biological network representing all the molecular interactions involved in capacitation was build and analyzed, then, an experimental set up was carried out to confirm the computational model-based prediction.ResultsThe analysis of computational model pointed out that the "actin polymerization" node had some important and unique features:- it is one of the most connected nodes,- it links in a specific manner all the intracellular compartments,- its removal from the network did not affect the global network topology but caused the loss of five important nodes (and among them the "plasma membrane" and "outer acrosome membrane" fusion).Thus, it was suggested that actin polymerization could be involved in the signaling coordination of different subcellular districts, and that its functional ablation could compromise spermatozoa ability to complete the capacitation (while the main signaling pathway remained unaffected). The experiments, carried out inhibiting the actin polymerization in capacitating boar spermatozoa by the administration of cytocalasin D (CD), demonstrated that the CD treatment inhibited spermatozoa ability to reach the full fertilizing ability, while, the examined signaling pathways (membrane acquisition of chlortetracicline pattern C, protein tyrosine phosphorylation, phospholipase C-γ1 relocalization, intracellular calcium response to zonae pellucidae) remained effective, thus, confirming the model-based hypothesis.ConclusionsThe model based-hypothesis was confirmed by the reported data obtained with the in vitro experiments, which strengthen the idea that the actin cytoskeleton is not only a mechanical support for the cell, but that it exerts a key role in signaling during the sperm capacitation.
Highlights
The signalling cascades involved in many biological processes require the coordination of different subcellular districts
The model based-hypothesis was confirmed by the reported data obtained with the in vitro experiments, which strengthen the idea that the actin cytoskeleton is a mechanical support for the cell, but that it exerts a key role in signaling during the sperm capacitation
More interesting is the behaviour of the “actin polymerization” node, represented in Figure 1, that links a smaller number of nodes (8) located in all the subcellular compartments
Summary
The signalling cascades involved in many biological processes require the coordination of different subcellular districts. One of the most important events in the history of life was the eukaryotes evolution that started with the onset of intracellular compartmentalization, approximately 1.62.1 billion years ago [1] This fundamental step had enormous consequences on cell organization and function. “We already have signaling “wires” distinguished by the identity of the molecules in the pathways Compartmentalization duplicates these existing wires and separates them in space. The interpretation of the molecular mechanisms involved in cell signaling is made possible by new computational approaches that allow to modellize cellular functions as a network of integrated and coordinated signals operating within subcellular districts interconnected to each other [3,4]. The spermatozoa offer several advantages to adopt this kind of approach since:
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