A Flagellar A-Kinase Anchoring Protein with Two Amphipathic Helices Forms a Structural Scaffold in the Radial Spoke Complex

A-kinase anchoring proteins (AKAPs) contain an amphipathic helix (AH) that binds the dimerization and docking (D/D) domain, RIIa, in cAMP-dependent protein kinase A (PKA). Many AKAPs were discovered solely based on the AH–RIIa interaction in vitro. An RIIa or a similar Dpy-30 domain is also present in numerous diverged molecules that are implicated in critical processes as diverse as flagellar beating, membrane trafficking, histone methylation, and stem cell differentiation, yet these molecules remain poorly characterized. Here we demonstrate that an AKAP, RSP3, forms a dimeric structural scaffold in the flagellar radial spoke complex, anchoring through two distinct AHs, the RIIa and Dpy-30 domains, in four non-PKA spoke proteins involved in the assembly and modulation of the complex. Interestingly, one AH can bind both RIIa and Dpy-30 domains in vitro. Thus, AHs and D/D domains constitute a versatile yet potentially promiscuous system for localizing various effector mechanisms. These results greatly expand the current concept about anchoring mechanisms and AKAPs

Type 1 IP3 receptors activate BKCa channels via local molecular coupling in arterial smooth muscle cells

Plasma membrane large-conductance Ca2+-activated K+ (BKCa) channels and sarcoplasmic reticulum inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are expressed in a wide variety of cell types, including arterial smooth muscle cells. Here, we studied BKCa channel regulation by IP3 and IP3Rs in rat and mouse cerebral artery smooth muscle cells. IP3 activated BKCa channels both in intact cells and in excised inside-out membrane patches. IP3 caused concentration-dependent BKCa channel activation with an apparent dissociation constant (Kd) of ∼4 µM at physiological voltage (−40 mV) and intracellular Ca2+ concentration ([Ca2+]i; 10 µM). IP3 also caused a leftward-shift in BKCa channel apparent Ca2+ sensitivity and reduced the Kd for free [Ca2+]i from ∼20 to 12 µM, but did not alter the slope or maximal Po. BAPTA, a fast Ca2+ buffer, or an elevation in extracellular Ca2+ concentration did not alter IP3-induced BKCa channel activation. Heparin, an IP3R inhibitor, and a monoclonal type 1 IP3R (IP3R1) antibody blocked IP3-induced BKCa channel activation. Adenophostin A, an IP3R agonist, also activated BKCa channels. IP3 activated BKCa channels in inside-out patches from wild-type (IP3R1+/+) mouse arterial smooth muscle cells, but had no effect on BKCa channels of IP3R1-deficient (IP3R1−/−) mice. Immunofluorescence resonance energy transfer microscopy indicated that IP3R1 is located in close spatial proximity to BKCa α subunits. The IP3R1 monoclonal antibody coimmunoprecipitated IP3R1 and BKCa channel α and β1 subunits from cerebral arteries. In summary, data indicate that IP3R1 activation elevates BKCa channel apparent Ca2+ sensitivity through local molecular coupling in arterial smooth muscle cells

Asthma: Cytokine-Induced Over-Expression of Matrix Metalloproteases Compromises Airway Epithelium Tight Junctions and a Clinical Case Study

The University of Nevada, Reno Libraries will promptly respond to removal requests related to content that violates intellectual property laws, data protections, or has been uploaded without creator consent. Takedown notices should be directed to our ScholarWolf team ([email protected]) with information about the object, including its full URL and the nature of your complaint.Asthma is a chronic respiratory disease that results in a constriction of the airways. While there is no known cause of the disease, one possible theory of the molecular cause of asthma is that the tight junctions of the airway epithelium are disrupted as a result of cytokine activity that up regulates expression of matrix metalloprotease 9. MMP9 encourages detachment-induced cell death�"anoikis�"which results in a structural change compromising the airway epithelium’s ability to act as a primary immune defense mechanism. The chronic characterization of asthma results because of an ineffective epithelial repair mechanism which prevents full recovery of the affected airway tissues thus allowing for further aggravation by environmental pathogens. Further investigation of this pathway could potentially allow for improvement in treatment and perhaps even the identification of a cure. First, a detailed background of the disease will be introduced in chapter 1. The following chapter will provide a literature review focused on the mechanism by which matrix metalloprotease 9 results in a compromised airway epithelium (and thus increased susceptibility to environmental pathogens). Lastly, chapter 3 will comprise of a clinical case study regarding the diagnosis and treatment of asthma

Le pain des larmes : récit / Charles Mauban

Contient une table des matièresAvec mode text

[catalog] Notice des estampes et dessins anciens et modernes provenant de la collection de feu M. Georges Mauban.

GeannoteerdBijzondere collectie

L'Acétonurie, sa valeur sémiologique, son traitement, par le Dr Henri Mauban,...

Contient une table des matièresAvec mode text