Abstract
Pancreatic β-cells, residents of the islets of Langerhans, are the unique insulin-producers in the body. Their physiology is a topic of intensive studies aiming to understand the biology of insulin production and its role in diabetes pathology. However, investigations about these cells’ subset of secreted proteins, the secretome, are surprisingly scarce and a list describing islet/β-cell secretome upon glucose-stimulation is not yet available. In silico predictions of secretomes are an interesting approach that can be employed to forecast proteins likely to be secreted. In this context, using the rationale behind classical secretion of proteins through the secretory pathway, a Python tool capable of predicting classically secreted proteins was developed. This tool was applied to different available proteomic data (human and rodent islets, isolated β-cells, β-cell secretory granules, and β-cells supernatant), filtering them in order to selectively list only classically secreted proteins. The method presented here can retrieve, organize, search and filter proteomic lists using UniProtKB as a central database. It provides analysis by overlaying different sets of information, filtering out potential contaminants and clustering the identified proteins into functional groups. A range of 70–92% of the original proteomes analyzed was reduced generating predicted secretomes. Islet and β-cell signal peptide-containing proteins, and endoplasmic reticulum-resident proteins were identified and quantified. From the predicted secretomes, exemplary conservational patterns were inferred, as well as the signaling pathways enriched within them. Such a technique proves to be an effective approach to reduce the horizon of plausible targets for drug development or biomarkers identification.
Highlights
The term secretome was first defined as the whole subset of factors secreted by a cell [1] and later revised to ‘all proteins secreted by the cell into the extracellular space’ [2]
Proteins are secreted through the secretory pathway [4]. mRNAs are processed by ribosomes in the cytoplasm and the proteins containing a signal peptide (SP) – motif often composed by one positively charged amino acid followed by 6–12 hydrophobic amino acids [5] – are cotranslationally translocated to the endoplasmic reticulum (ER) [6]
This signal is commonly a tetrapeptide – K D E L – or related sequences [8,9] and enables proteins to bind to lysine–aspartic acid–glutamic acid–leucine (KDEL)-receptors at the early Golgi, preventing proteins from being secreted from cells [10]
Summary
The term secretome was first defined as the whole subset of factors secreted by a cell [1] and later revised to ‘all proteins secreted by the cell into the extracellular space’ [2]. These factors can regulate a multitude of physiological processes and dictate the composition of the extracellular environment. The ER has its own subset of native proteins, the so-called ER-resident proteins [8] Their continuous localization to the ER lumen is secured by an ER-retrieval signal located in the C-terminal part of the protein [8]. This signal is commonly a tetrapeptide – K (lysine/lys) D (aspartic acid/asp) E (glutamic acid/glu) L (leucine/leu) – or related sequences [8,9] and enables proteins to bind to KDEL-receptors at the early Golgi, preventing proteins from being secreted from cells [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
