Prion protein regulates glutamate-dependent lactate transport of astrocytes.
Prion-related protein (PrP) is a neural cell adhesion molecule involved in neurite outgrowth, neuronal survival, and synaptic function. In search of novel binding partners for PrP, we identified the alpha2/beta2-Na+/K+-ATPase and showed that this astroglial ATPase interacts directly with the immunoglobulin superfamily adhesion molecule basigin. In cultured astrocytes, PrP is involved in regulating lactate transport via the astroglial monocarboxylate transporter 1 (MCT1) and in conjunction with alpha2/beta2-ATPase and basigin. Lactate transport via MCT1 is glutamate dependent and regulated by glutamate receptor 2 (GluR2)-containing AMPA receptors with which PrP interacts. The functional interplay between PrP, GluR2, alpha2/beta2-ATPase, basigin, and MCT1 in regulating lactate transport of astrocytes may be functional in the metabolic cross talk between astrocytes and neurons, most likely under stress.
Kleene
Ralf
R
Zentrum für Molekulare Neurobiologie, Universität Hamburg, 20246 Hamburg, Germany.
Loers
Gabriele
G
Langer
Julia
J
Frobert
Yveline
Y
Buck
Friedrich
F
Schachner
Melitta
M
D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism*; D051926:Basigin / Q000378:metabolism / Q000502:physiology; D002478:Cells, Cultured; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology*; D019344:Lactic Acid / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism / Q000502:physiology; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D011328:Prions / Q000378:metabolism / Q000502:physiology*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism / Q000502:physiology; D027981:Symporters / Q000378:metabolism / Q000502:physiology; D000099233:Monocarboxylate Transport Protein 1
D051926:Basigin; D018698:Glutamic Acid; D019344:Lactic Acid; D027501:Monocarboxylic Acid Transporters; D011328:Prions; D018091:Receptors, AMPA; D000254:Sodium-Potassium-Exchanging ATPase; D027981:Symporters; D000099233:Monocarboxylate Transport Protein 1; C104722:glutamate receptor ionotropic, AMPA 2