About this Research Topic
Regulated Intramembrane Proteolysis (RIP) is a tightly controlled 2-step process in which transmembrane proteins are cleaved. In the initial step, called ectodomain shedding, cleavage near the membrane leads to the release of the extracellular domain. This cleavage thus regulates surface expression of various membrane proteins, e.g. receptors, hence modulating cellular sensitivity for environmental stimuli or other intrinsic cell functions. On the other hand, many released ectodomains have (ant)agonistic functions acting in an autocrine or paracrine manner. In some cases, ectodomain shedding is followed intramembrane proteolysis, thereby releasing the intracellular domain which can act as a transcription factor, which is well known to be required for the cell fate regulator Notch.
In the last two decades, evidence for the role of RIP in vascular biology and cardiovascular/metabolic diseases, including heart failure, atherosclerosis and its co-morbidities has been emerging and the list of identified substrates is ever increasing. RIP is implicated in various crucial processes, such as angiogenesis, inflammation, wound healing/tissue repair/fibrosis and thrombosis. Considering the wide variety of substrates and cellular functions controlled by RIP, it is of vital importance to maintain its proper function for homeostasis. Much attention nowadays is focusing on the complex regulatory mechanisms that control RIP, including chaperone proteins, membrane fluidity and membrane nanodomains. Such information, especially on disease- or cell-specific regulatory mechanisms that control substrate specificity, would be important for the development of more selective therapeutic strategies to restore derailed RIP function in disease.
In this Research Topic, we welcome original research from basic science reports to clinical studies as well as overview contributions that advance our understanding of the regulation and function of intramembrane proteolysis in the field of vascular biology. We also encourage methodology papers (either reviews for various methods or reports of new methods) e.g. to specifically detect or quantify proteolytic activities or to identify RIP substrates. Submissions on molecular mechanisms and functional consequences of RIP will be considered in as far as related to the specialty section Atherosclerosis and Vascular Medicine of Frontiers in Cardiovascular Medicine.
Keywords: Ectodomain shedding, intramembrane proteolysis, vascular biology, cardiovascular diseases, co-morbidities
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.