A cut above (and below): Protein cleavage in the regulation of polycystin trafficking and signaling.

Valeria Padovano, Kavita Mistry, David Merrick, Nikolay Gresko, Michael J Caplan

Cellular signalling 2020 Aug

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The polycystin-1 and 2 proteins, encoded by the genes mutated in Autosomal Dominant Polycystic Kidney Disease, are connected to a large number of biological pathways. While the nature of these connections and their relevance to the primary functions of the polycystin proteins have yet to be fully elucidated, it is clear that many of them are mediated by or depend upon cleavage of the polycystin-1 protein. Cleavage of polycystin-1 at its G protein coupled receptor proteolytic site is an obligate step in the protein's maturation and in aspects of its trafficking. This cleavage may also serve to prime polycystin-1 to play a role as a non-canonical G protein coupled receptor. Cleavage of the cytoplasmic polycystin-1C terminal tail releases fragments that are able to enter the nucleus and the mitochondria and to influence their activities. Understanding the nature of these cleavages, their regulation and their consequences is likely to provide valuable insights into both the physiological functions served by the polycystin proteins and the pathological consequences of their absence. Copyright © 2020 Elsevier Inc. All rights reserved.

Citation

Valeria Padovano, Kavita Mistry, David Merrick, Nikolay Gresko, Michael J Caplan. A cut above (and below): Protein cleavage in the regulation of polycystin trafficking and signaling. Cellular signalling. 2020 Aug;72:109634