Role of Chromogranin A and its derived peptides in the context of gut physiology

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Functions of the gastrointestinal (GI) tract are in part orchestrated by a host of peptide hormones produced and released from various cell types within the GI system. Despite the wealth of knowledge accumulated on the role of peptides in gut biology, it is almost certain that there are additional peptides with significant physiological activities in gut. The primary function of the intestine is the absorption and propulsion of dietary nutrients, but it also forms a physical and immunological barrier. During the last decade, a new type of protein, discovered initially at the adrenal gland, has revolutionized our thinking of the neuroendocrine regulation of the immune system. This new granin protein called Chromogranin (Cg) A has defined a new paradigm on how neuroendocrine and physiological mechanisms are regulated. The granin family of proteins is stored in chromaffin granules of some neurons present in the gut level, as well as specific types of endocrine, immune and neuroendocrine cells present at the gut wall. Cell and tissue specific CgA has been described in the GI tract, generating small peptides. However, it is not fully understood which specific small peptides are present at the gut level and how they affect gastrointestinal physiological functions, in particular smooth muscle contraction and permeability. In this research program, we propose to extend our knowledge to elucidate the presence and the physiological actions of these peptides, with a focus on their potential regulation of gut smooth muscle contraction and trans-epithelial permeability. We believe that these innovative and novel studies will allow us to expand our knowledge of the cellular and molecular mechanism involved in CgA-derived peptides mediated permeability and smooth muscle functions, explain roles as a key regulators of cellular function and help understand the role of neuroendocrine peptides on gut physiology. This will have a great impact in gut physiology as it will open new avenues for other teams to describe in a deeper approach the interaction between CgA cells and intracellular pathways.