title: Lactate flux in astrocytes is enhanced by a non-catalytic action of carbonic anhydrase II.
abstract: Rapid exchange of metabolites between different cell types is crucial for energy homeostasis of the brain. Besides glucose, lactate is a major metabolite in the brain and is primarily produced in astrocytes. In the present study, we report that carbonic anhydrase 2 (CAII) enhances both influx and efflux of lactate in mouse cerebellar astrocytes. The augmentation of lactate transport is independent of the enzyme's catalytic activity, but requires direct binding of CAII to the C-terminal of the monocarboxylate transporter MCT1, one of the major lactate/proton cotransporters in astrocytes and most tissues. By employing its intramolecular proton shuttle, CAII, bound to MCT1, can act as a ‘proton collecting antenna' for the transporter, suppressing the formation of proton microdomains at the transporter-pore and thereby enhancing lactate flux. By this mechanism CAII could enhance transfer of lactate between astrocytes and neurons and thus provide the neurons with an increased supply of energy substrate.
authors.affiliation: Division of General Zoology, Department of Biology, University of Kaiserslautern, PO Box 3049, D-67653 Kaiserslautern, Germany.
authors.forename: Malin H
authors.initials: MH
authors.lastname: Stridh
authors.forename: Marco D
authors.initials: MD
authors.lastname: Alt
authors.forename: Sarah
authors.initials: S
authors.lastname: Wittmann
authors.forename: Hella
authors.initials: H
authors.lastname: Heidtmann
authors.forename: Mayank
authors.initials: M
authors.lastname: Aggarwal
authors.forename: Brigitte
authors.initials: B
authors.lastname: Riederer
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
authors.forename: Gunther
authors.initials: G
authors.lastname: Wennemuth
authors.forename: Robert
authors.initials: R
authors.lastname: McKenna
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Deitmer
authors.forename: Holger M
authors.initials: HM
authors.lastname: Becker
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D024402:Carbonic Anhydrase II / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000378:metabolism*; D005260:Female; D019344:Lactic Acid / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D027501:Monocarboxylic Acid Transporters / Q000235:genetics / Q000378:metabolism*; D009865:Oocytes; D034741:RNA, Small Interfering / Q000235:genetics; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D024402:Carbonic Anhydrase II; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D034741:RNA, Small Interfering; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1