Stabilization of ubiquitous mitochondrial creatine kinase preprotein by APP family proteins.
Amyloid precursor protein (APP) is involved in the pathogenesis of Alzheimer's disease (AD). However, the physiological role of APP and its family members is still unclear. To gain insights into APP function, we used a proteomic approach to identify APP interacting proteins. We report here for the first time a direct interaction between the C-terminal region of APP family proteins and ubiquitous mitochondrial creatine kinase (uMtCK). This interaction was confirmed in vitro as well as in cultured cells and in brain. Interestingly, expression of full-length and C-terminal domain of APP family proteins stabilized uMtCK preprotein in cultured cells. Our data suggest that APP may regulate cellular energy levels and mitochondrial function via a direct interaction and stabilization of uMtCK.
Li
Xiaofan
X
Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
Bürklen
Tanja
T
Yuan
Xianglin
X
Schlattner
Uwe
U
Desiderio
Dominic M
DM
Wallimann
Theo
T
Homayouni
Ramin
R
D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D001923:Brain Chemistry; D019556:COS Cells; D002522:Chlorocebus aethiops; D052281:Creatine Kinase, Mitochondrial Form / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020543:Proteome
D016564:Amyloid beta-Protein Precursor; D007527:Isoenzymes; D010446:Peptide Fragments; D011498:Protein Precursors; D020543:Proteome; D052281:Creatine Kinase, Mitochondrial Form