Katrina Viloria and Natasha Hill recently published a review article in the journal ‘Biomolecular Concepts’ entitled ‘Embracing the complexity of matricellular proteins: the functional and clinical significance of splice variation’. Katrina explains what the paper is about:
“The extracellular matrix is a network of proteins that provides structural support and information to cells about their environment. A family of proteins knowns as Matricellular proteins regulate the matrix and control fundamental cellular processes such as adhesion, growth, migration, and differentiation. Alternative splicing is a normal process that allows cells to produce different versions of each protein in the body. This involves cutting, or splicing, the mRNA that encodes proteins in different ways. However, very little is currently known about alternative splicing of matricellular proteins. We used a bioinformatics approach to examine this question and found evidence for a large number of matricellular splice variants – over twice as many variants per gene as the average across the genome. Some of these variants are likely to have different matrix binding properties and therefore distinct functions. Interestingly, we also found evidence of variants lacking the signal peptide that tags the protein for secretion into the extracellular space. These variants are therefore likely to be intracellular, which may explain a longstanding mystery as to why these supposedly secreted proteins can sometimes be seen inside the cell. Matricellular proteins are also known to be important in diseases such as cancer and diabetes, and we discuss the potential application of matricellular splice variants as diagnostic biomarkers. Overall, the review highlights the importance of understanding the complexity of matricellular proteins to make sense of their role in disease and to apply this knowledge clinically”.