GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:19295159

From GONUTS
Jump to: navigation, search
Citation

Mayer, F, Mayer, N, Chinn, L, Pinsonneault, RL, Kroetz, D and Bainton, RJ (2009) Evolutionary conservation of vertebrate blood-brain barrier chemoprotective mechanisms in Drosophila. J. Neurosci. 29:3538-50

Abstract

Pharmacologic remedy of many brain diseases is difficult because of the powerful drug exclusion properties of the blood-brain barrier (BBB). Chemical isolation of the vertebrate brain is achieved through the highly integrated, anatomically compact and functionally overlapping chemical isolation processes of the BBB. These include functions that need to be coordinated between tight diffusion junctions and unidirectionally acting xenobiotic transporters. Understanding of many of these processes has been hampered, because they are not well mimicked by ex vivo models of the BBB and have been experimentally difficult and expensive to disentangle in intact rodent models. Here we show that the Drosophila melanogaster (Dm) humoral/CNS barrier conserves the xenobiotic exclusion properties found in the vertebrate vascular endothelium. We characterize a fly ATP binding cassette (ABC) transporter, Mdr65, that functions similarly to mammalian xenobiotic BBB transporters and show that varying its levels solely in the Dm BBB changes the inherent sensitivity of the barrier to cytotoxic pharmaceuticals. Furthermore, we demonstrate orthologous function between Mdr65 and vertebrate ABC transporters by rescuing chemical protection of the Dm brain with human MDR1/Pgp. These data indicate that the ancient origins of CNS chemoprotection extend to both conserved molecular means and functionally analogous anatomic spaces that together promote CNS selective drug partition. Thus, Dm presents an experimentally tractable system for analyzing physiological properties of the BBB in an intact organism.

Links

PubMed PMC3040577 Online version:10.1523/JNEUROSCI.5564-08.2009

Keywords

ATP-Binding Cassette Transporters/genetics; ATP-Binding Cassette Transporters/metabolism; Animals; Animals, Genetically Modified; Blood-Brain Barrier/drug effects; Blood-Brain Barrier/metabolism; Cell Line; Drosophila Proteins/genetics; Drosophila Proteins/metabolism; Drosophila melanogaster/genetics; Drosophila melanogaster/physiology; Drug Delivery Systems; Evolution, Molecular; Humans; Neuroprotective Agents/metabolism; P-Glycoprotein/metabolism; P-Glycoproteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:MDR65

enables

GO:0008559: ABC-type xenobiotic transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:MDR65

involved_in

GO:0042908: xenobiotic transport

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:MDR65

enables

GO:0015562: efflux transmembrane transporter activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

DROME:MDR65

part_of

GO:0043190: ATP-binding cassette (ABC) transporter complex

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:MDR65

located_in

GO:0005919: pleated septate junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:MDR65

involved_in

GO:0060857: establishment of glial blood-brain barrier

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:MOODY

located_in

GO:0005919: pleated septate junction

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.