Membrane phospholipid control of nucleotide sensitivity of KATP channels.
It is proposed that membrane-incorporated PIPs can bind to positive charges in the cytoplasmic region of the KATP channel's Kir6.2 subunit, stabilizing the open state of the channel and antagonizing the inhibitory effect of ATP.
Adenosine Diphosphate as an Intracellular Regulator of Insulin Secretion
By binding to SUR NBF2 and antagonizing ATP inhibition of KATP channels, intracellular MgADP may regulate insulin secretion.
Genotype and phenotype correlations in 417 children with congenital hyperinsulinism.
- K. Snider, S. Becker, A. Ganguly
- Medicine, BiologyJournal of Clinical Endocrinology and Metabolism
- 1 February 2013
Genotype to phenotype correlations were most successful in children with GLUD1, GCK, and recessive KATP mutations, because such defects might be either recessive or dominant and, if dominant, be either responsive or unresponsive to diazoxide.
Regulation of KATP Channel Activity by Diazoxide and MgADP
A model in which SUR1 sensitizes the KATP channel to ATP inhibition, and nucleotide hydrolysis at the nucleotide binding folds blocks this effect is proposed, and MgADP and diazoxide are proposed to stabilize this desensitized state of the channel.
Octameric Stoichiometry of the KATP Channel Complex
ATP-sensitive potassium (KATP) channels link cellular metabolism to electrical activity in nerve, muscle, and endocrine tissues. They are formed as a functional complex of two unrelated subunits—a…
Cryo-EM structure of the ATP-sensitive potassium channel illuminates mechanisms of assembly and gating
The SUR1-ABC core is found in an unusual inward-facing conformation whereby the two nucleotide binding domains are misaligned along a two-fold symmetry axis, revealing a possible mechanism by which glibenclamide inhibits channel activity.
A prion protein cycles between the cell surface and an endocytic compartment in cultured neuroblastoma cells.
Sulfated Glycans Stimulate Endocytosis of the Cellular Isoform of the Prion Protein, PrPC, in Cultured Cells (*)
The results raise the possibility that sulfated glycans inhibit prion production by altering the cellular localization of PrPC precursor, and they indicate that endogenous proteoglycans are likely to play an important role in the cellular metabolism of both PrPC and PrPSc.
A glycolipid-anchored prion protein is endocytosed via clathrin-coated pits
It is proposed that the polypeptide chain of chPrP associates with the extracellular domain of a transmembrane protein that contains a coated pit internalization signal, and is reduced by 70% after neuroblastoma cells are incubated in hypertonic medium, a treatment that inhibits endocytosis by disrupting clathrin lattices.
Structural Determinants of Pip2 Regulation of Inward Rectifier KATP Channels
The regions and residues defined in this study parallel those uncovered in recent studies of PIP2 sensitivity in other inward rectifier channels, indicating a common structural basis for PIP1 regulation.