UNASSIGNED: @entity671 receptors ( @entity4335 ) are a family of ubiquitously expressed intracellular @entity141 release channels. Regulation of channel activity by @entity141 , @entity2036 , phosphorylation, protein binding partners and other cellular factors is thought to play a major role in defining the specific spatiotemporal characteristics of intracellular @entity141 signals. These properties are, in turn, believed pivotal for the selective and specific physiological activation of @entity141 dependent effectors. @entity4335 are also substrates for the intracellular @entity462 proteases, calpain and caspase. Cleavage of the @entity4335 has been proposed to play a role in apoptotic cell death by uncoupling regions important for IP3 binding from the channel domain, leaving an unregulated leaky @entity141 pore. Contrary to this hypothesis, we demonstrate following proteolysis that N- and C-termini of @entity4335 remain associated, presumably through non-covalent interactions. Further, we show that complementary fragments of @entity4335 assemble into tetrameric structures and retain their ability to be regulated robustly by IP3 . While peptide continuity is clearly not necessary for IP3 -gating of the channel, we propose that cleavage of the @entity4335 peptide chain may alter other important regulatory events to modulate channel activity. In this scenario, stimulation of the cleaved @entity4335 may support distinct spatiotemporal @entity141 signals and activation of specific effectors. Notably, in many adaptive physiological events, the non-apoptotic activities of caspase and caplain are demonstrated to be important, but the substrates of the proteases are poorly defined. We speculate that @entity1949 may represent a novel form of @entity4335 regulation, which plays a role in varied adaptive physiological processes. This article is protected by copyright. All rights reserved.

@entity1949 of XXXX Receptors: A novel mechanism regulating channel activity?

@entity671 :: ('MESH:D015544', 'Chemical') :: ['Inositol 1,4,5-trisphosphate'] @entity1949 :: ('MESH:D012892', 'Disease') :: ['proteolytic fragmentation'] @entity462 :: ('MESH:D003545', 'Chemical') :: ['cysteine'] @entity2036 :: ('MESH:D009711', 'Chemical') :: ['nucleotides'] @entity4335 :: ('3708', 'Gene') :: ['IP3 R', 'IP3 R1'] @entity141 :: ('CHEBI:29108', 'Chemical') :: ['Ca(2+)']
@entity671 :: (MESH:D015544,Chemical) :: ['inositol 1,4,5-trisphosphate']
