Dimensional Crossover of Localisation and Delocalisation in a Quantum Hall Bar

The 2-- to 1--dimensional crossover of the localisation length of electrons confined to a disordered quantum wire of finite width $L_y$ is studied in a model of electrons moving in the potential of uncorrelated impurities. An analytical formula for the localisation length is derived, describing the dimensional crossover as function of width $L_y$, conductance $g$ and perpendicular magnetic field $B$ . On the basis of these results, the scaling analysis of the quantum Hall effect in high Landau levels, and the delocalisation transition in a quantum Hall wire are reconsidered.Comment: 12 pages, 7 figure

Identification of a region at the N-terminus of phospholipase C-beta 3 that interacts with G protein beta gamma subunits

Members of the phospholipase C-β (PLC-β) family of proteins are activated either by Gα or Gβγ subunits of heterotrimeric G proteins. To define specific regions of PLC-β3 that are involved in binding and activation by Gβγ, a series of fragments of PLC-β3 as glutathione-S-transferase (GST) fusion proteins were produced. A fragment encompassing the N-terminal pleckstrin homology (PH) domain and downstream sequence (GST-N) bound to G protein β1γ2 in an in vitro binding assay, and binding was inhibited by G protein α subunit, Gαi1. This PLC-β3 fragment also inhibited Gβγ-stimulated PLC-β activity in a reconstitution system, while having no significant effect on Gαq-stimulated PLC-β3 activity. The N-terminal Gβγ binding region was delineated further to the first 180 amino acids, and the sequence Asn150−Ser180, just distal to the PH domain, was found to be required for the interaction. Mutation of basic residues 154Arg, 155Lys, 159Lys, and 161Lys to Glu within this region reduced Gβγ binding affinity and specifically reduced the EC50 for Gβγ-dependent activation of the mutant enzyme 3-fold. Basal activity and Gαq-dependent activation of the enzyme were unaffected by the mutations. While these basic residues may not directly mediate the interaction with Gβγ, the data provide evidence for an N-terminal Gβγ binding region of PLC-β3 that is involved in activation of the enzyme

M3 muscarinic receptor interaction with phospholipase C beta3 determines its signaling efficiency

Contains fulltext : 133821.pdf (publisher's version ) (Open Access)Phospholipase Cbeta (PLCbeta) enzymes are activated by G protein-coupled receptors through receptor-catalyzed guanine nucleotide exchange on Galphabetagamma heterotrimers containing Gq family G proteins. Here we report evidence for a direct interaction between M3 muscarinic receptor (M3R) and PLCbeta3. Both expressed and endogenous M3R interacted with PLCbeta in coimmunoprecipitation experiments. Stimulation of M3R with carbachol significantly increased this association. Expression of M3R in CHO cells promoted plasma membrane localization of YFP-PLCbeta3. Deletion of the PLCbeta3 C terminus or deletion of the PLCbeta3 PDZ ligand inhibited coimmunoprecipitation with M3R and M3R-dependent PLCbeta3 plasma membrane localization. Purified PLCbeta3 bound directly to glutathione S-transferase (GST)-fused M3R intracellular loops 2 and 3 (M3Ri2 and M3Ri3) as well as M3R C terminus (M3R/H8-CT). PLCbeta3 binding to M3Ri3 was inhibited when the PDZ ligand was removed. In assays using reconstituted purified components in vitro, M3Ri2, M3Ri3, and M3R/H8-CT potentiated Galphaq-dependent but not Gbetagamma-dependent PLCbeta3 activation. Disruption of key residues in M3Ri3N and of the PDZ ligand in PLCbeta3 inhibited M3Ri3-mediated potentiation. We propose that the M3 muscarinic receptor maximizes the efficiency of PLCbeta3 signaling beyond its canonical role as a guanine nucleotide exchange factor for Galpha

Positional cloning uncovers mutations in PLCE1 responsible for a nephrotic syndrome variant that may be reversible

Nephrotic syndrome, a malfunction of the kidney glomerular filter, leads to proteinuria, edema and, in steroid-resistant nephrotic syndrome, end-stage kidney disease. Using positional cloning, we identified mutations in the phospholipase C epsilon gene (PLCE1) as causing early-onset nephrotic syndrome with end-stage kidney disease. Kidney histology of affected individuals showed diffuse mesangial sclerosis (DMS). Using immunofluorescence, we found PLCepsilon1 expression in developing and mature glomerular podocytes and showed that DMS represents an arrest of normal glomerular development. We identified IQ motif–containing GTPase-activating protein 1 as a new interaction partner of PLCepsilon1. Two siblings with a missense mutation in an exon encoding the PLCepsilon1 catalytic domain showed histology characteristic of focal segmental glomerulosclerosis. Notably, two other affected individuals responded to therapy, making this the first report of a molecular cause of nephrotic syndrome that may resolve after therapy. These findings, together with the zebrafish model of human nephrotic syndrome generated by plce1 knockdown, open new inroads into pathophysiology and treatment mechanisms of nephrotic syndrome