Increased spectrin proteolysis in the brindled mouse brain.
Proteolytically generated fragments of the microfilament anchoring protein brain spectrin were found to accumulate in brindled mouse brain. Proteolysis was most extensive in brain regions possessing high concentrations of N-methyl-D-aspartate (NMDA) receptors (e.g. cortex, striatum, hippocampus). The brindle mutation affects copper homeostasis and thus a variety of copper-dependent enzymes needed in intermediary metabolism. The altered mitochondria of these mice are suggested to less efficiently buffer NMDA receptor-gated calcium fluxes, thus promoting activation of calcium-activated proteases and subsequent degradation of the spectrin meshwork.
Seubert
P
P
Bonney Center for the Neurobiology of Learning and Memory, University of California, Irvine 92717.
Peterson
C
C
Vanderklish
P
P
Cotman
C
C
Lynch
G
G
D000375:Aging / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D003300:Copper / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains / Q000254:growth & development / Q000378:metabolism*; D008970:Molecular Weight; D013049:Spectrin / Q000378:metabolism*
D013049:Spectrin; D003300:Copper