Sayak Banerjee, Amity University Kolkata
Protein secretion is a physiological process taking place in eukaryotes for the firm regulation of a vast number of primary biological tasks including homeostasis, cell and tissue development, cell division, differentiation, and other complex biochemical processes. It is of key importance without which cellular communications are incomplete. Generally, proteins that are targeted for secretion hold a signal peptide or leader peptide. This peptide sequence determines the fate of the protein or where the protein will be localized and enables the proteins for its progress through the typical ER/Golgi-dependant pathway.
In this pathway, the signal peptide is required to transport the budding proteins into the ER lumen. From there the proteins are delivered to the Golgi body and eventually they reach the cell surface by way of vesicular transport. Often, a major amount of proteins lack the signal peptide sequence at their N-terminus which restricts them from following the usual pathway. Some unconventional pathways are found to facilitate the secretion of proteins that are devoid of the leader peptide. This type of unconventional secretion of proteins can occur in two ways, vesicular pathways and non-vesicular pathways. Proteins that are liberated directly into the extracellular space follow the non-vesicular pathway whereas, proteins that are liberated within vesicles are said to follow the vesicular pathway.
The proteins are secreted out to the extracellular surroundings with the usage of various vesicular structures, most of which are identified as exosomes. Exosomes are microvesicles playing an essential role in cell-cell communication. They are around 30 nm to 100 nm in size, and function in the movement and transportation of proteins, nucleic acids, and lipids from one cell to another. An exosome is produced in the cytoplasm itself by the inward folding of the outer layer of the endosome which is in its late stage. This gives rise to a large-sized multivesicular body (MVB) within which there are present many intraluminal vesicles (ILV). As the fusion between the MVB and the plasma membrane takes place, a huge amount of ILV gets secreted out into the extracellular space in the form of exosomes. These exosomes not only comprise diverse luminal cargo proteins including nuclear and cytosolic proteins in which the signal peptide is absent, but also transmembrane proteins.
Exosomes have been seen to be involved in a variety of biological processes including health and diseases, such as coordination of inflammation and blood clotting. Scientists have observed that the exosome content might alter under many pathological circumstances like cardiovascular diseases, neurodegenerative diseases, and cancer. The researchers from the Department of Immunomedicine of the Complutense University of Madrid used this biological significance of exosomes and their function in the unconventional protein secretion pathway to establish their study in the BMC Bioinformatics journal.
They said that there are quite a few bioinformatics tools that can be used to identify and predict proteins secreted by these unconventional vesicular pathways. These tools namely, OutCyte, SecretomeP, SecretP, and SPRED are based on machine learning models but not for specifically predicting protein secretion by exosomes. The proteins secreted by the exosomes are highly heterogeneous with the absence of any sequence pattern, which allows them to be identified. In this study, the researchers have presented ExoPred, a bioinformatics tool that specifically identifies the protein, without a signal peptide or transmembrane regions, secreted by exosomes. ExoPred works based on the Random Forest (RF) model trained on dipeptide composition of exosome proteins. This web-based tool achieved 75.53% precision in an individual dataset which only included leaderless proteins from the vertebra.
Therefore, the prediction and annotation of a particular protein involved in the unconventional vesicular pathway imply the relevance of exosomes as major vehicles in secreting leaderless proteins. This is characteristic towards a promising role in cell-cell communication as well as it open ups to unexplored functions. Concerning this, the scientists have also publicized a standalone version of ExoPred for resources and bioinformaticians providing protein sequence annotations.
Also read: A Viral DNA-packaging Motor Mechanism
Reference:
- Ras-Carmona, A., Gomez-Perosanz, M., & Reche, P. A. (2021). Prediction of unconventional protein secretion by exosomes. BMC bioinformatics, 22(1), 333. https://doi.org/10.1186/s12859-021-04219-z
- The Corrosion Prediction from the Corrosion Product Performance
- Nitrogen Resilience in Waterlogged Soybean plants
- Cell Senescence in Type II Diabetes: Therapeutic Potential
- Transgene-Free Canker-Resistant Citrus sinensis with Cas12/RNP
- AI Literacy in Early Childhood Education: Challenges and Opportunities
4 thoughts on “Exosomes predicted to carry out protein secretion”