WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, May 17, 2006, 26(20):5411-5419; doi:10.1523/JNEUROSCI.5500-05.2006

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (26)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Qu, Z.
Right arrow Articles by Hartzell, H. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Qu, Z.
Right arrow Articles by Hartzell, H. C.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CYSTEINE
*Genetics Home Reference

 Previous Article  |  Next Article 

Cellular/Molecular
The Anion-Selective Pore of the Bestrophins, a Family of Chloride Channels Associated with Retinal Degeneration

Zhiqiang Qu, Li-Ting Chien, Yuanyuan Cui, and H. Criss Hartzell

Department of Cell Biology and Center for Neurodegenerative Disease, Emory University School of Medicine, Atlanta, Georgia 30322

Correspondence should be addressed to H. Criss Hartzell, Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, 535 Whitehead Building, Atlanta, GA 30322-3030. Email: criss.hartzell{at}emory.edu

Mutations in human bestrophin-1 (VMD2) are genetically linked to a juvenile form of macular degeneration and autosomal dominant vitreoretinochoroidopathy. Recently, it has been proposed that bestrophins are Cl– channels and that the putative second transmembrane domain participates in forming the bestrophin pore. However, the structural determinants of Cl– ion permeation through the channel pore are not known. Here we systematically replaced every amino acid in mouse bestrophin-2 (mBest2) between positions 69 and 104 with cysteine. We then measured the effects on the relative permeability and conductance of the channel to Cl– and SCN– (thiocyanate) and determined the accessibility of the cysteine-substituted amino acids to extracellularly applied, membrane-impermeant sulfhydryl reagents. Unlike K+ channels, the amino acids forming the mBest2 selectivity filter are not discretely localized but are distributed over ~20 amino acids within the transmembrane domain. Cysteine-substituted amino acids in the selectivity filter are easily accessible to extracellularly applied sulfhydryl reagents and select for anionic sulfhydryl reagents over cationic ones. Understanding the structure of the anion conduction pathway of bestrophins provides insights into how mutations produce channel dysfunction and may provide important information for development of therapeutic strategies for treating macular degeneration.

Key words: ion channel; anion channel; chloride channel; macular degeneration; bestrophin; patch clamp

Received Dec. 22, 2005; revised March 9, 2006; accepted April 7, 2006.

Correspondence should be addressed to H. Criss Hartzell, Department of Cell Biology, Emory University School of Medicine, 615 Michael Street, 535 Whitehead Building, Atlanta, GA 30322-3030. Email: criss.hartzell{at}emory.edu




This article has been cited by other articles:


Home page
 J. Neurosci.Home page
H. Park, S.-J. Oh, K.-S. Han, D. H. Woo, H. Park, G. Mannaioni, S. F. Traynelis, and C. J. Lee
Bestrophin-1 Encodes for the Ca2+-Activated Anion Channel in Hippocampal Astrocytes
J. Neurosci., October 14, 2009; 29(41): 13063 - 13073.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Qu, W. Cheng, Y. Cui, Y. Cui, and J. Zheng
Human Disease-causing Mutations Disrupt an N-C-terminal Interaction and Channel Function of Bestrophin 1
J. Biol. Chem., June 12, 2009; 284(24): 16473 - 16481.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
Q. Xiao, A. Prussia, K. Yu, Y.-y. Cui, and H. C. Hartzell
Regulation of Bestrophin Cl Channels by Calcium: Role of the C Terminus
J. Gen. Physiol., December 1, 2008; 132(6): 681 - 692.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
K. E. O'Driscoll, W. J. Hatton, H. R Burkin, N. Leblanc, and F. C. Britton
Expression, localization, and functional properties of Bestrophin 3 channel isolated from mouse heart
Am J Physiol Cell Physiol, December 1, 2008; 295(6): C1610 - C1624.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
L.-T. Chien and H. C. Hartzell
Rescue of Volume-regulated Anion Current by Bestrophin Mutants with Altered Charge Selectivity
J. Gen. Physiol., November 1, 2008; 132(5): 537 - 546.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
Z. Qu and H. C. Hartzell
Bestrophin Cl- channels are highly permeable to HCO3-
Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1371 - C1377.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
K. Yu, Q. Xiao, G. Cui, A. Lee, and H. C. Hartzell
The Best Disease-Linked Cl- Channel hBest1 Regulates CaV1 (L-type) Ca2+ Channels via src-Homology-Binding Domains
J. Neurosci., May 28, 2008; 28(22): 5660 - 5670.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
B. Bakall, P. McLaughlin, J. B. Stanton, Y. Zhang, H. C. Hartzell, L. Y. Marmorstein, and A. D. Marmorstein
Bestrophin-2 Is Involved in the Generation of Intraocular Pressure
Invest. Ophthalmol. Vis. Sci., April 1, 2008; 49(4): 1563 - 1570.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
H. C. Hartzell, Z. Qu, K. Yu, Q. Xiao, and L.-T. Chien
Molecular Physiology of Bestrophins: Multifunctional Membrane Proteins Linked to Best Disease and Other Retinopathies
Physiol Rev, April 1, 2008; 88(2): 639 - 672.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
L.-T. Chien and H. C. Hartzell
Drosophila Bestrophin-1 Chloride Current Is Dually Regulated by Calcium and Cell Volume
J. Gen. Physiol., October 29, 2007; 130(5): 513 - 524.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
K. Yu, Z. Qu, Y. Cui, and H. C. Hartzell
Chloride Channel Activity of Bestrophin Mutants Associated with Mild or Late-Onset Macular Degeneration
Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4694 - 4705.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Z. Q. Qu, K. Yu, Y. Y. Cui, C. Ying, and C. Hartzell
Activation of Bestrophin Cl- Channels Is Regulated by C-terminal Domains
J. Biol. Chem., June 15, 2007; 282(24): 17460 - 17467.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. M. Milenkovic, A. Rivera, F. Horling, and B. H. F. Weber
Insertion and Topology of Normal and Mutant Bestrophin-1 in the Endoplasmic Reticulum Membrane
J. Biol. Chem., January 12, 2007; 282(2): 1313 - 1321.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
K. Yu, Y. Cui, and H. C. Hartzell
The Bestrophin Mutation A243V, Linked to Adult-Onset Vitelliform Macular Dystrophy, Impairs Its Chloride Channel Function
Invest. Ophthalmol. Vis. Sci., November 1, 2006; 47(11): 4956 - 4961.
[Abstract] [Full Text] [PDF]

Home page
 JGPHome page
L.-T. Chien, Z.-R. Zhang, and H. C. Hartzell
Single Cl- Channels Activated by Ca2+ in Drosophila S2 Cells Are Mediated By Bestrophins
J. Gen. Physiol., August 28, 2006; 128(3): 247 - 259.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Pifferi, G. Pascarella, A. Boccaccio, A. Mazzatenta, S. Gustincich, A. Menini, and S. Zucchelli
Bestrophin-2 is a candidate calcium-activated chloride channel involved in olfactory transduction
PNAS, August 22, 2006; 103(34): 12929 - 12934.
[Abstract] [Full Text] [PDF]


-
-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-