Expression of Drosophila melanogaster P-glycoproteins is associated with ATP channel activity

Irene Bosch, George R. Jackson, James Croop, Horacio F. Cantiello

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Two distinct Drosophila melanogaster P-glycoprotein (Pgp) gene homologues of different chromosomal origin, MDR49 and MDR65, have been previously identified (38). Most Pgps are implicated in the development of the multidrug-resistance phenotype. Despite intense efforts to identify the molecular mechanism(s) associated with Pgp function, the endogenous substrate(s) of these transport molecules is largely unknown. Recent studies from our laboratory indicate that a murine Pgp homologue (E. H. Abraham, A. G. Prat, L. Gerweck, T. Seneveratne, R. J. Arceci, R. Kramer, G. Guidotti, and H. F. Cantiello. Proc. Natl. Acad. Sci. USA 90: 312-316, 1993) and a related protein, the cystic fibrosis transmembrane conductance regulator (CFTR; I. L. Reisin, A. Prat, E. H. Abraham, J. F. Amara, R. J. Gregory, D. A. Ausiello, and H. F. Cantiello. J. Biol. Chem. 269: 20584-20591, 1994), are novel ATP-permeable ion channels. The common feature of these two proteins is the conserved ATP-binding cassettes (ABC); thus molecules structurally linked to the ABC transporter family may be also functionally associated with ATP channel activity. In this study, MDR65 and MDR49 Pgps were functionally expressed in Sf9 cells, and patch-clamp techniques were applied to assess the role of these proteins in the electrodiffusional movement of ATP. In the presence of intracellular ATP and external NaCl, expression of MDR65 was associated with a linear electrodiffusional pathway that was permeable to both ATP and Cl-. Under symmetrical ATP conditions, only voltage depolarization activated a MDR65-mediated ATP-conductive pathway. Expression of MDR49 was also associated with a voltage-activated ATP conductance in symmetrical ATP, but no apparent permeability to either Cl- or ATP was observed under asymmetrical conditions. The different functional properties of MDR65 and MDR49 may be indicative of distinct physiological roles in this organism. The study indicates, however, that the two Drosophila Pgp homologues share strong functional similarities with their mammalian relatives Pgp and CFTR.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume271
Issue number5 40-5
StatePublished - Nov 1996
Externally publishedYes

Fingerprint

P-Glycoproteins
Drosophila melanogaster
Adenosine Triphosphate
P-Glycoprotein
Sf9 Cells
Cystic Fibrosis Transmembrane Conductance Regulator
Proteins
Molecules
ATP-Binding Cassette Transporters
Depolarization
Clamping devices
Multiple Drug Resistance
Electric potential
Patch-Clamp Techniques
Ion Channels
Drosophila
Permeability
Genes

Keywords

  • adenosine 5'- triphosphate release
  • baculovirus
  • multidrug-resistance gene products
  • Sf9 cells

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Expression of Drosophila melanogaster P-glycoproteins is associated with ATP channel activity. / Bosch, Irene; Jackson, George R.; Croop, James; Cantiello, Horacio F.

In: American Journal of Physiology - Cell Physiology, Vol. 271, No. 5 40-5, 11.1996.

Research output: Contribution to journalArticle

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