Abstract

description): This competitive renewal application proposes to further examine the structural, cellular and genetic mechanisms of MaxiK channel function. The main hypothesis centers on the idea that maxiK function is regulated by beta subunit association. The questions to be addressed include the following. 1) How do the alpha subunit domains move during activation and how do the beta subunits influence this movement? 2) How do tyrosine kinases influence alpha/beta interaction? 3) What is the structure of the alpha subunit C-terminus? 4) What are the signals for apical sorting of the alpha subunit? 5) What is the impact of deleting the alpha and/or beta subunits from a transgenic mouse? The proposed specific aims are: 1) Define the movement of different regions of the alpha subunit using fluorescent probes, and their modification by the beta 1 subunit. 2) Investigate the mechanism of c-Src modulation of alpha/beta complexes. 3) Perform large-scale purification of the alpha subunit carboxyl end with the goal to crystallize it. 4) Investigate the alpha/beta subunit polarized sorting in MDCK cells. 5) Obtain alpha and beta knockout mice and investigate the impact on neuronal and vascular tissues.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL054970-06
Application #
6194800
Study Section
Cardiovascular and Pulmonary Research A Study Section (CVA)
Project Start
1995-08-17
Project End
2005-07-31
Budget Start
2000-09-26
Budget End
2001-07-31
Support Year
6
Fiscal Year
2000
Total Cost
$344,250
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Singh, Harpreet; Lu, Rong; Rodriguez, Pedro Felipe Gardeazabal et al. (2012) Visualization and quantification of cardiac mitochondrial protein clusters with STED microscopy. Mitochondrion 12:230-6
Morera, Francisco J; Alioua, Abderrahmane; Kundu, Pallob et al. (2012) The first transmembrane domain (TM1) of ýý2-subunit binds to the transmembrane domain S1 of ýý-subunit in BK potassium channels. FEBS Lett 586:2287-93
Danesh, Shahab M; Kundu, Pallob; Lu, Rong et al. (2011) Distinct transcriptional regulation of human large conductance voltage- and calcium-activated K+ channel gene (hSlo1) by activated estrogen receptor alpha and c-Src tyrosine kinase. J Biol Chem 286:31064-71
Alioua, Abderrahmane; Li, Min; Wu, Yong et al. (2011) Unconventional myristoylation of large-conductance Ca²?-activated K? channel (Slo1) via serine/threonine residues regulates channel surface expression. Proc Natl Acad Sci U S A 108:10744-9
Bopassa, Jean Chrisostome; Eghbali, Mansoureh; Toro, Ligia et al. (2010) A novel estrogen receptor GPER inhibits mitochondria permeability transition pore opening and protects the heart against ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 298:H16-23
Wu, Yong; Eghbali, Mansoureh; Ou, Jimmy et al. (2010) Quantitative determination of spatial protein-protein correlations in fluorescence confocal microscopy. Biophys J 98:493-504
Li, Min; Tanaka, Yoshio; Alioua, Abderrahmane et al. (2010) Thromboxane A2 receptor and MaxiK-channel intimate interaction supports channel trans-inhibition independent of G-protein activation. Proc Natl Acad Sci U S A 107:19096-101
Saito, Tomoaki; Ciobotaru, Andrea; Bopassa, Jean Chrisostome et al. (2009) Estrogen contributes to gender differences in mouse ventricular repolarization. Circ Res 105:343-52
Bukiya, Anna N; Vaithianathan, Thirumalini; Toro, Ligia et al. (2009) Channel beta2-4 subunits fail to substitute for beta1 in sensitizing BK channels to lithocholate. Biochem Biophys Res Commun 390:995-1000
Ou, J W; Kumar, Y; Alioua, A et al. (2009) Ca2+- and thromboxane-dependent distribution of MaxiK channels in cultured astrocytes: from microtubules to the plasma membrane. Glia 57:1280-95

Showing the most recent 10 out of 49 publications