Loss of G2 subunit of vacuolar-type proton transporting ATPase leads to G1 subunit upregulation in the brain.
Vacuolar-type ATPase (V-ATPase) is a primary proton pump with versatile functions in various tissues. In nerve cells, V-ATPase is required for accumulation of neurotransmitters into secretory vesicles and subsequent release at the synapse. Neurons express a specific isoform (G2) of the G subunit of V-ATPase constituting the catalytic sector of the enzyme complex. Using gene targeting, we generated a mouse lacking functional G2 (G2 null), which showed no apparent disorders in architecture and behavior. In the G2-null mouse brain, a G1 subunit isoform, which is ubiquitously expressed in neuronal and non-neuronal tissues, accumulated more abundantly than in wild-type animals. This G1 upregulation was not accompanied by an increase in mRNA. These results indicate that loss of function of neuron-specific G2 isoform was compensated by an increase in levels of the G1 isoform without apparent upregulation of the G1 mRNA.
Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kohdo, Kyotanabe, Kyoto 610-0395, Japan.
Nobuyuki
N
Kawamura
Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kohdo, Kyotanabe, Kyoto 610-0395, Japan.
Ge-Hong
GH
Sun-Wada
Division of Biological Sciences, Institute of Scientific and Industrial Research, Osaka University, Mihogaoka 8-1, Ibaraki, Osaka 567-0047, Japan.
Yoh
Y
Wada
D000818:Animals; D001921:Brain / Q000378:metabolism*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D018390:Gene Targeting; D056426:Genetic Loci; D005838:Genotype; D007668:Kidney / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000378:metabolism; D020033:Protein Isoforms; D021122:Protein Subunits / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D015854:Up-Regulation; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D020033:Protein Isoforms; D021122:Protein Subunits; D012333:RNA, Messenger; D025262:Vacuolar Proton-Translocating ATPases