Blagoy Blagoev

Quantitative Proteomics for Investigation of Secreted Factors: Focus on Muscle Secretome

The response of cells to even slight changes in the cellular microenvironment determines the reaction of the whole organism and its ability to adapt to macroenvironmental alterations. Generally, it is well recognized that the communication between cells, tissues, and organs is critical for the maintenance of the entire body homeostasis. The different cell types that build the various organs and tissues have an enormous potential to produce proteins that once secreted in the extracellular space exert their action in an auto-, paraand/or endocrine manner. It is estimated that out of the total 20.500 protein-coding genes in human, approximately 10% encode secreted proteins (Clamp et al., 2007; Skalnikova et al., 2011). The separate and combinatorial action of these ~2200 secreted proteins can influence the biology not only at adjacent sites but also have a clear effect on the whole organism (Lin et al., 2008). The secreted factors, which can range from large proteins to short peptides, are divided into different groups or classes according to their structural properties and function. The prototypical secreted proteins are represented by the group of proteins found in the blood stream and other body fluids, the components of the extracellular matrix (ECM) and enzymes released in the intestine and stomach. An intriguing group of secreted factors comprise cell surface receptor ligands, such as hormones, growth factors, and cytokines. These proteins can exert their actions either on a limited number of responsive tissues or can act on virtually all cell types dependent on the expression of their specific receptors. It is essential to decipher in depth the signaling events that are triggered by the various hormones and growth factors to understand the general mechanisms of the biological processes that occur in a strictly controlled fashion in both space and time. The processes that secreted factors influence and directly regulate range from cellular differentiation, growth and survival to apoptosis, autophagy, and ageing. In addition, a growth factor can often exert a divergent and even opposite effect depending on the cell type and cellular state. Taken in consideration the role of secreted factors in directing biological processes, malfunction of the signaling cascades orchestrated by secreted factors can have severe consequences and lead to development of a series of complicated diseases and disorders (Flier, 2001; Pedersen, 2009; Walsh, 2009). Therefore, a comprehensive characterization of secreted molecules by different cellular subtypes, tissues, and organs can contribute to the elucidation of the physiological state of a given organism and to the determination of the