spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
Development ePress online publication date 22 Mar 2006
doi: 10.1242/dev.02341

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.02341v1
133/9/1657    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
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 Google Scholar
Google Scholar
Right arrow Articles by Adams, D. S.
Right arrow Articles by Levin, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Adams, D. S.
Right arrow Articles by Levin, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Research article

Early, H+-V-ATPase-dependent proton flux is necessary for consistent left-right patterning of non-mammalian vertebrates


Dany S. Adams, Kenneth R. Robinson, Takahiro Fukumoto, Shipeng Yuan, R. Craig Albertson, Pamela Yelick, Lindsay Kuo, Megan McSweeney, and Michael Levin*
* Author for correspondence (e-mail: mlevin{at}forsyth.org)

Biased left-right asymmetry is a fascinating and medically important phenomenon. We provide molecular genetic and physiological characterization of a novel, conserved, early, biophysical event that is crucial for correct asymmetry: H+ flux. A pharmacological screen implicated the H+-pump H+-V-ATPase in Xenopus asymmetry, where it acts upstream of early asymmetric markers. Immunohistochemistry revealed an actin-dependent asymmetry of H+-V-ATPase subunits during the first three cleavages. H+-flux across plasma membranes is also asymmetric at the four- and eight-cell stages, and this asymmetry requires H+-V-ATPase activity. Abolishing the asymmetry in H+ flux, using a dominant-negative subunit of the H+-V-ATPase or an ectopic H+ pump, randomized embryonic situs without causing any other defects. To understand the mechanism of action of H+-V-ATPase, we isolated its two physiological functions, cytoplasmic pH and membrane voltage (Vmem) regulation. Varying either pH or Vmem, independently of direct manipulation of H+-V-ATPase, caused disruptions of normal asymmetry, suggesting roles for both functions. V-ATPase inhibition also abolished the normal early localization of serotonin, functionally linking these two early asymmetry pathways. The involvement of H+-V-ATPase in asymmetry is conserved to chick and zebrafish. Inhibition of the H+-V-ATPase induces heterotaxia in both species; in chick, H+-V-ATPase activity is upstream of Shh; in fish, it is upstream of Kupffer's vesicle and Spaw expression. Our data implicate H+-V-ATPase activity in patterning the LR axis of vertebrates and reveal mechanisms upstream and downstream of its activity. We propose a pH- and Vmem-dependent model of the early physiology of LR patterning.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:


Home page
 J. Cell Sci.Home page
C. D. McCaig, B. Song, and A. M. Rajnicek
Electrical dimensions in cell science
J. Cell Sci., December 1, 2009; 122(23): 4267 - 4276.
[Abstract] [Full Text] [PDF]

Home page
 Poult. Sci.Home page
B. Kang, J. R. Guo, H. M. Yang, R. J. Zhou, J. X. Liu, S. Z. Li, and C. Y. Dong
Differential expression profiling of ovarian genes in prelaying and laying geese
Poult. Sci., September 1, 2009; 88(9): 1975 - 1983.
[Abstract] [Full Text] [PDF]

Home page
 IOVSHome page
R. J. Nuckels, A. Ng, T. Darland, and J. M. Gross
The Vacuolar-ATPase Complex Regulates Retinoblast Proliferation and Survival, Photoreceptor Morphogenesis, and Pigmentation in the Zebrafish Eye
Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 893 - 905.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
S. Aw and M. Levin
Is left-right asymmetry a form of planar cell polarity?
Development, February 1, 2009; 136(3): 355 - 366.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. Morokuma, D. Blackiston, D. S. Adams, G. Seebohm, B. Trimmer, and M. Levin
Modulation of potassium channel function confers a hyperproliferative invasive phenotype on embryonic stem cells
PNAS, October 28, 2008; 105(43): 16608 - 16613.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
A. Garic-Stankovic, M. Hernandez, G. R. Flentke, M. H. Zile, and S. M. Smith
A ryanodine receptor-dependent Cai2+ asymmetry at Hensen's node mediates avian lateral identity
Development, October 1, 2008; 135(19): 3271 - 3280.
[Abstract] [Full Text] [PDF]

Home page
 JDRHome page
A.-S. Tseng and M. Levin
Tail Regeneration in Xenopus laevis as a Model for Understanding Tissue Repair
Journal of Dental Research, September 1, 2008; 87(9): 806 - 816.
[Abstract] [Full Text] [PDF]

Home page
 Phil Trans R Soc BHome page
C. M Freisinger, I. Schneider, T. A Westfall, and D. C Slusarski
Calcium dynamics integrated into signalling pathways that influence vertebrate axial patterning
Phil Trans R Soc B, April 12, 2008; 363(1495): 1377 - 1385.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Biol.Home page
J. Zuo, S. Vergara, S. Kohno, and L. S. Holliday
Biochemical and functional characterization of the actin-binding activity of the B subunit of yeast vacuolar H+-ATPase
J. Exp. Biol., April 1, 2008; 211(7): 1102 - 1108.
[Abstract] [Full Text] [PDF]

Home page
 Plant CellHome page
A. C. Certal, R. B. Almeida, L. M. Carvalho, E. Wong, N. Moreno, E. Michard, J. Carneiro, J. Rodriguez-Leon, H.-M. Wu, A. Y. Cheung, et al.
Exclusion of a Proton ATPase from the Apical Membrane Is Associated with Cell Polarity and Tip Growth in Nicotiana tabacum Pollen Tubes
PLANT CELL, March 1, 2008; 20(3): 614 - 634.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
I. Schneider, D. W. Houston, M. R. Rebagliati, and D. C. Slusarski
Calcium fluxes in dorsal forerunner cells antagonize -catenin and alter left-right patterning
Development, January 1, 2008; 135(1): 75 - 84.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
X. Shu, J. Huang, Y. Dong, J. Choi, A. Langenbacher, and J.-N. Chen
Na,K-ATPase {alpha}2 and Ncx4a regulate zebrafish left-right patterning
Development, May 15, 2007; 134(10): 1921 - 1930.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
D. S. Adams, A. Masi, and M. Levin
H+ pump-dependent changes in membrane voltage are an early mechanism necessary and sufficient to induce Xenopus tail regeneration
Development, April 1, 2007; 134(7): 1323 - 1335.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
M. V. Danilchik, E. E. Brown, and K. Riegert
Intrinsic chiral properties of the Xenopus egg cortex: an early indicator of left-right asymmetry?
Development, November 15, 2006; 133(22): 4517 - 4526.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2006