Batten disease and the control of the Fo subunit c pore by cGMP and calcium.
Subunit c of ATP synthase functions as a high conductance ion channel, tightly regulated by calcium. We have suggested that the pathogenesis of Batten syndromes involving overaccumulation of subunit c are linked to the protein's ion channel function. In normal electrically excitable tissue the channel could act as a pacer setting nodal voltage via control of cation entry. The channel conductance is controlled by voltage, calcium, cyclic nucleotides and polyamines. We discuss the pathogenic role that subunit c could play in the electrically excitable tissues of retina, brain and heart where Batten neurodegeneration is seen. Focus is given to potential links between subunit c and the known mutant gene products in the Batten diseases, the process of apoptosis, and the requirement of the growing brain for gradients of cGMP, a ligand of the subunit c channel.
McGeoch
J E
JE
Department of Molecular and Cellular Biology, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA. mcgeoch@fas.harvard.edu
Guidotti
G
G
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology; D008854:Microscopy, Electron; D025261:Mitochondrial Proton-Translocating ATPases; D009410:Nerve Degeneration / Q000378:metabolism; D009472:Neuronal Ceroid-Lipofuscinoses / Q000378:metabolism*; D006180:Proton-Translocating ATPases / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D012756:Sheep
C103607:mitochondrial ATPase subunit c; D025261:Mitochondrial Proton-Translocating ATPases; D006180:Proton-Translocating ATPases; D006152:Cyclic GMP; D002118:Calcium