|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 34, 30591-30597, August 23, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Bestrophin is a 68-kDa basolateral plasma
membrane protein expressed in retinal pigment epithelial cells (RPE).
It is encoded by the VMD2 gene, which is mutated in Best
macular dystrophy, a disease characterized by a depressed light peak in
the electrooculogram. Recently it was proposed that bestrophin
is a chloride channel responsible for generating the light peak. To
investigate its function further, we immunoaffinity purified a
bestrophin complex from RPE lysates and identified bestrophin and the
The nucleotide sequence(s) reported in this paper has been submitted to the GenBankTM/EBI Data Bank with accession number(s) AY064707.
Bestrophin Interacts Physically and Functionally with Protein
Phosphatase 2A*
,,,,§, and§¶
Department of Ophthalmic Research, Cole Eye
Institute, and the § Department of Cell Biology, Lerner
Research Institute, The Cleveland Clinic Foundation,
Cleveland, Ohio 44195
-catalytic subunit of protein phosphatase 2A (PP2A) as members of
the complex by matrix-assisted laser desorption ionization
time-of-flight mass spectrometry. Protein-protein interaction between
bestrophin and PP2Ac and the structural subunit of PP2A, PR65, was
confirmed by reciprocal immunoprecipitation. The C-terminal cytoplasmic domain of bestrophin was sufficient for the interaction with PP2A as
demonstrated by a pulldown assay using a fusion of this domain with
glutathione S-transferase. Bestrophin was phosphorylated when expressed in RPE-J cells and this phosphorylation was sensitive to
okadaic acid. Purified PP2A effectively dephosphorylated bestrophin in vitro. These data suggest that bestrophin is in the
signal transduction pathway that modulates the light peak of the
electrooculogram, that it is regulated by phosphorylation, and that
phosphorylation of bestrophin is in turn regulated by PP2A.
*
This work was supported by National Institutes of Health
Grants R01 EY13160 (to A. D. M.) and R01 EY06603 (to J. W. C.), a Kirchgessner Foundation research grant (to A. D. M.), and the Foundation Fighting Blindness (to J. W. C.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 P. J. McLaughlin, B. Bakall, J. Choi, Z. Liu, T. Sasaki, E. C. Davis, A. D. Marmorstein, and L. Y. Marmorstein Lack of fibulin-3 causes early aging and herniation, but not macular degeneration in mice Hum. Mol. Genet., December 15, 2007; 16(24): 3059 - 3070. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. N. A. Mandal, V. Vasireddy, G. B. Reddy, X. Wang, S. E. Moroi, B. R. Pattnaik, B. A. Hughes, J. R. Heckenlively, P. F. Hitchcock, M. M. Jablonski, et al. CTRP5 Is a Membrane-Associated and Secretory Protein in the RPE and Ciliary Body and the S163R Mutation of CTRP5 Impairs Its Secretion Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5505 - 5513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Lecuona, L. A. Dada, H. Sun, M. L. Butti, G. Zhou, T.-L. Chew, and J. I. Sznajder Na,K-ATPase {alpha}1-subunit dephosphorylation by protein phosphatase 2A is necessary for its recruitment to the plasma membrane FASEB J, December 1, 2006; 20(14): 2618 - 2620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. McLaughlin, Q. Chen, M. Horiguchi, B. C. Starcher, J. B. Stanton, T. J. Broekelmann, A. D. Marmorstein, B. McKay, R. Mecham, T. Nakamura, et al. Targeted disruption of fibulin-4 abolishes elastogenesis and causes perinatal lethality in mice. Mol. Cell. Biol., March 1, 2006; 26(5): 1700 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ayyagari, M. N. A. Mandal, A. J. Karoukis, L. Chen, N. C. McLaren, M. Lichter, D. T. Wong, P. F. Hitchcock, R. C. Caruso, S. E. Moroi, et al. Late-Onset Macular Degeneration and Long Anterior Lens Zonules Result from a CTRP5 Gene Mutation Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3363 - 3371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Strauss The Retinal Pigment Epithelium in Visual Function Physiol Rev, July 1, 2005; 85(3): 845 - 881. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Loewen and G. W. Forsyth Structure and Function of CLCA Proteins Physiol Rev, July 1, 2005; 85(3): 1061 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Campos, V. Forjaz, L. R. Kozak, E. Silva, and M. Castelo-Branco Quantitative Phenotyping of Chromatic Dysfunction in Best Macular Dystrophy Arch Ophthalmol, July 1, 2005; 123(7): 944 - 949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Tsunenari, H. Sun, J. Williams, H. Cahill, P. Smallwood, K.-W. Yau, and J. Nathans Structure-Function Analysis of the Bestrophin Family of Anion Channels J. Biol. Chem., October 17, 2003; 278(42): 41114 - 41125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Bakall, L. Y. Marmorstein, G. Hoppe, N. S. Peachey, C. Wadelius, and A. D. Marmorstein Expression and Localization of Bestrophin during Normal Mouse Development Invest. Ophthalmol. Vis. Sci., August 1, 2003; 44(8): 3622 - 3628. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |