Details

Autor(en) / Beteiligte

• Kerkhofs, Martijn
• Seitaj, Bruno
• Ivanova, Hristina
• Monaco, Giovanni
• Bultynck, Geert
• Parys, Jan B

Titel

Pathophysiological consequences of isoform-specific IP 3 receptor mutations

Ist Teil von

• Biochimica et biophysica acta. Molecular cell research, 2018-11, Vol.1865 (11 Pt B), p.1707

Ort / Verlag

Netherlands

Erscheinungsjahr

2018

Link zum Volltext

Quelle

Elsevier ScienceDirect Journals Complete

Beschreibungen/Notizen

• Ca signaling governs a diverse range of cellular processes and, as such, is subject to tight regulation. A main component of the complex intracellular Ca -signaling network is the inositol 1,4,5-trisphosphate (IP ) receptor (IP R), a tetrameric channel that mediates Ca release from the endoplasmic reticulum (ER) in response to IP . IP R function is controlled by a myriad of factors, such as Ca , ATP, kinases and phosphatases and a plethora of accessory and regulatory proteins. Further complexity in IP R-mediated Ca signaling is the result of the existence of three main isoforms (IP R1, IP R2 and IP R3) that display distinct functional characteristics and properties. Despite their abundant and overlapping expression profiles, IP R1 is highly expressed in neurons, IP R2 in cardiomyocytes and hepatocytes and IP R3 in rapidly proliferating cells as e.g. epithelial cells. As a consequence, dysfunction and/or dysregulation of IP R isoforms will have distinct pathophysiological outcomes, ranging from neurological disorders for IP R1 to dysfunctional exocrine tissues and autoimmune diseases for IP R2 and -3. Over the past years, several IP R mutations have surfaced in the sequence analysis of patient-derived samples. Here, we aimed to provide an integrative overview of the clinically most relevant mutations for each IP R isoform and the subsequent molecular mechanisms underlying the etiology of the disease.