Region-specific proteolysis differentially regulates type 1 inositol 1,4,5-trisphosphate receptor activity.

The Journal of Biological Chemistry
Liwei WangDavid I Yule

Abstract

The inositol 1,4,5 trisphosphate receptor (IP3R) is an intracellular Ca2+ release channel expressed predominately on the membranes of the endoplasmic reticulum. IP3R1 can be cleaved by caspase or calpain into at least two receptor fragments. However, the functional consequences of receptor fragmentation are poorly understood. Our previous work has demonstrated that IP3R1 channels, formed following either enzymatic fragmentation or expression of the corresponding complementary polypeptide chains, retain tetrameric architecture and are still activated by IP3 binding despite the loss of peptide continuity. In this study, we demonstrate that region-specific receptor fragmentation modifies channel regulation. Specifically, the agonist-evoked temporal Ca2+ release profile and protein kinase A modulation of Ca2+ release are markedly altered. Moreover, we also demonstrate that activation of fragmented IP3R1 can result in a distinct functional outcome. Our work suggests that proteolysis of IP3R1 may represent a novel form of modulation of IP3R1 channel function and increases the repertoire of Ca2+ signals achievable through this channel.

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Citations

Feb 13, 2019·Cold Spring Harbor Perspectives in Biology·David L Prole, Colin W Taylor
Oct 28, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Xiuye CaoWenbin Zhong
Nov 16, 2019·Annual Review of Physiology·Kozo Hamada, Katsuhiko Mikoshiba
Jun 15, 2019·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Elena PanizzaAnita Aperia
Dec 6, 2019·World Journal of Gastroenterology : WJG·Fernanda de Oliveira LemosM Fatima Leite
May 16, 2021·Biochimica Et Biophysica Acta. Molecular Cell Research·Alberto DanesePaolo Pinton
Dec 24, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·John J BassettGregory R Monteith

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