Submitted on July 27, 2006
Accepted on January 29, 2007
The Drosophila dMRP4 regulates responsiveness to O2 deprivation and development under hypoxia
He Huang1 and Gabriel G. Haddad2*
1 Pediatrics, University of California, San Diego, San Diego, California, United States
2 Pediatrics, University of California, San Diego, La Jolla, California, United States
* To whom correspondence should be addressed. E-mail: ghaddad{at}ucsd.edu.
For most vertebrates, oxygen is a prerequisite for survival. Although we have previously shown that Drosophila melanogaster is hypoxia-tolerant, how this species senses O2 deprivation and how it survives oxygen-limiting conditions is as yet poorly understood. We began to address this question by testing for anoxic responsiveness in Drosophila adult flies following overexpression of existing EP lines. In this screen, we identified Drosophila CG14709 gene as a homologue of the human multidrug resistance protein 4 (MRP4/ABCC4) that is tightly regulated to oxygen. Ubiquitous expression of dMRP4 in adult flies resulted in increased sensitivity to anoxia as they had longer recovery time from anoxic stupor. When exposed to 4% oxygen chronically (throughout its life span), constitutive expression of dMRP4 in larvae caused larval lethality due to growth arrest. Mutations of dMRP4 led to a hypersensitive response to acute anoxia in adult flies but had less impact on larval survival under chronic hypoxia as compared to dMRP4 overexpression. Selective expression of this gene in neurons, but not in glia or muscles, mirrored the same phenotype as the ubiquitous one. Thus, our data suggest novel roles for MRP in vivo: a) dMRP4 regulates the sensitivity to acute or chronic O2 deprivation, and b) dMRP expression in neurons is sufficient to induce the sensitivity to O2 in the whole organism.
