Search results for "Z domain"

PTEN recruitment controls synaptic and cognitive function in Alzheimer's models

2016

Dyshomeostasis of amyloid-β peptide (Aβ) is responsible for synaptic malfunctions leading to cognitive deficits ranging from mild impairment to full-blown dementia in Alzheimer's disease. Aβ appears to skew synaptic plasticity events toward depression. We found that inhibition of PTEN, a lipid phosphatase that is essential to long-term depression, rescued normal synaptic function and cognition in cellular and animal models of Alzheimer's disease. Conversely, transgenic mice that overexpressed PTEN displayed synaptic depression that mimicked and occluded Aβ-induced depression. Mechanistically, Aβ triggers a PDZ-dependent recruitment of PTEN into the postsynaptic compartment. Using a PTEN kno…

The Navier–Stokes equations in exterior Lipschitz domains: L -theory

2020

Abstract We show that the Stokes operator defined on L σ p ( Ω ) for an exterior Lipschitz domain Ω ⊂ R n ( n ≥ 3 ) admits maximal regularity provided that p satisfies | 1 / p − 1 / 2 | 1 / ( 2 n ) + e for some e > 0 . In particular, we prove that the negative of the Stokes operator generates a bounded analytic semigroup on L σ p ( Ω ) for such p. In addition, L p - L q -mapping properties of the Stokes semigroup and its gradient with optimal decay estimates are obtained. This enables us to prove the existence of mild solutions to the Navier–Stokes equations in the critical space L ∞ ( 0 , T ; L σ 3 ( Ω ) ) (locally in time and globally in time for small initial data).

The CFTR associated protein CAP70 interacts with the apical Cl-/HCO3- exchanger DRA in rabbit small intestinal mucosa.

2005

DRA (down regulated in adenoma) is an intestinal anion exchanger, acting in parallel with NHE3 to facilitate ileal and colonic NaCl absorption. Furthermore it is involved in small intestinal bicarbonate secretion. Because DRA has a PDZ interaction motif, which may influence its properties, we searched for DRA-interacting PDZ adapter proteins in the small intestine. Using an overlay assay with the recombinant DRA C-terminus as a ligand, a 70 kDa protein was labeled, which was restricted to the brush border membrane in rabbit duodenal and ileal mucosa and was not detected in the colon. Destruction of the C-terminal PDZ interaction motif abolished this band, suggesting a specific protein-prote…

The Functional Role of the Second NPXY Motif of the LRP1 β-Chain in Tissue-type Plasminogen Activator-mediated Activation of N-Methyl-D-aspartate Rec…

2008

The low density lipoprotein receptor-related protein 1 (LRP1) emerges to play fundamental roles in cellular signaling pathways in the brain. One of its prominent ligands is the serine proteinase tissue-type plasminogen activator (tPA), which has been shown to act as a key activator of neuronal mitogen-activated protein kinase pathways via the N-methyl-D-aspartate (NMDA) receptor. However, here we set out to examine whether LRP1 and the NMDA receptor might eventually act in a combined fashion to mediate tPA downstream signaling. By blocking tPA from binding to LRP1 using the receptor-associated protein, we were able to completely inhibit NMDA receptor activation. Additionally, inhibition of …

NG2-positive cells in CNS function and the pathological role of antibodies against NG2 in demyelinating diseases

2005

NG2 is expressed by a variety of immature glia in the CNS including oligodendrocyte progenitor cells, paranodal astrocytes and perisynaptic glia. The protein has a large extracellular domain with two LNS/Lam G domains at the N-terminus and a short intracellular tail with a PDZ-recognition domain at the C-terminus. Experiments suggest that the protein plays a role in migration. The PDZ protein GRIP was identified as an intracellular binding partner of NG2 in immature glial cells. A complex is formed between GRIP, NG2 and the AMPA class of glutamate receptors: this may position these glial receptors towards sites of neuronal glutamate release at synapses and during myelination. Identification…

The evolutionary history and tissue mapping of GPR123: specific CNS expression pattern predominantly in thalamic nuclei and regions containing large …

2007

The Adhesion family of G protein-coupled receptors (GPCRs) includes 33 receptors and is the second largest GPCR family. Most of these proteins are still orphans and fairly little is known of their tissue distribution and evolutionary context. We report the evolutionary history of the Adhesion family protein GPR123 as well as mapping of GPR123 mRNA expression in mouse and rat using in situ hybridization and real-time PCR, respectively. GPR123 was found to be well conserved within the vertebrate lineage, especially within the transmembrane regions and in the distal part of the cytoplasmic tail, containing a potential PDZ binding domain. The real-time PCR data indicates that GPR123 is predomin…

Characterization of the interaction between Actinin-Associated LIM Protein (ALP) and the rod domain of α-actinin

2009

Abstract Background The PDZ-LIM proteins are a family of signalling adaptors that interact with the actin cross-linking protein, α-actinin, via their PDZ domains or via internal regions between the PDZ and LIM domains. Three of the PDZ-LIM proteins have a conserved 26-residue ZM motif in the internal region, but the structure of the internal region is unknown. Results In this study, using circular dichroism and nuclear magnetic resonance (NMR), we showed that the ALP internal region (residues 107–273) was largely unfolded in solution, but was able to interact with the α-actinin rod domain in vitro, and to co-localize with α-actinin on stress fibres in vivo. NMR analysis revealed that the ti…

Lipschitz conditions,b-arcwise connectedness and conformal mappings

1982

On the best Lipschitz extension problem for a discrete distance and the discrete ∞-Laplacian

2012

Abstract This paper concerns the best Lipschitz extension problem for a discrete distance that counts the number of steps. We relate this absolutely minimizing Lipschitz extension with a discrete ∞-Laplacian problem, which arises as the dynamic programming formula for the value function of some e -tug-of-war games. As in the classical case, we obtain the absolutely minimizing Lipschitz extension of a datum f by taking the limit as p → ∞ in a nonlocal p -Laplacian problem.

Lipschitz operator ideals and the approximation property

2016

[EN] We establish the basics of the theory of Lipschitz operator ideals with the aim of recovering several classes of Lipschitz maps related to absolute summability that have been introduced in the literature in the last years. As an application we extend the notion and main results on the approximation property for Banach spaces to the case of metric spaces. (C) 2015 Elsevier Inc. All rights reserved.