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Cited by 269

The DOI matches its Crossref record; 99 of the 99 references it cites were found in a registry or an index.

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

Open access
Adams, Dany S., Robinson, Kenneth R., Fukumoto, Takahiro, Yuan, Shipeng, Albertson, R. Craig, Yelick, Pamela, Kuo, Lindsay, McSweeney, Megan, Levin, Michael·2006·Development
DOI 10.1242/dev.02341
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Abstract

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.

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Metadata

Authors
Adams, D. S., Robinson, K. R., Fukumoto, T., Yuan, S., Albertson, R. C., Yelick, P., Kuo, L., McSweeney, M., & Levin, M.
Venue
Development
Publisher
The Company of Biologists
Published
2006-05-01
Volume
133
Issue
9
Pages
1657-1671
ISSN
  • 0950-1991 (ISSN-L)
  • 1477-9129
DOI
10.1242/dev.02341
OpenAlex
W2095210629
Cited by
269
References
99
FWCI
6.63
Type
journal article
Language
en
Open access
green

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