Chaperone-like manner of human neuronal tau towards lactate dehydrogenase.
In our experiments, inactivation of lactate dehydrogenase (LDH, EC1.1.1.27) in the presence of human microtubule-associated tau is observably suppressed during thermal and guanidine hydrochloride (GdnHCl) denaturation. Kinetic studies show tau can prevent LDH from self-aggregation monitored by light scattering during thermal denaturation. On the other hand, neuronal tau promotes reactivation of LDH and suppresses self-aggregation of non-native LDH when GdnHCl solution is diluted. Furthermore, the reactivation yield of LDH decreases significantly with delayed addition of tau. All experiments were completed in the reducing buffer with 1 mM DTT to avoid between tau and LDH forming the covalent bonds during unfolding and refolding. Thus, Tau prevents proteins from misfolding and aggregating into insoluble, nonfunctional inclusions and assists them to refold to reach the stable native state by binding to the exposed hydrophobic patches on proteins instead of by forming or breaking covalent bonds. Additionally, tau remarkably enhances reactivation of GDH (glutamic dehydrogenase, EC 1.4.1.3), another carbohydrate metabolic enzyme, also showing a chaperone-like manner. It suggests that neuronal tau non-specifically functions a chaperone-like protein towards the enzymes of carbohydrate metabolism.
Tian
Rui
R
Laboratory of Visual Information Processing, Center for Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China.
Nie
Chun-Lai
CL
He
Rong-Qiao
RQ
D000818:Animals; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D019791:Guanidine / Q000737:chemistry; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D018832:Molecular Chaperones / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D011817:Rabbits; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D018832:Molecular Chaperones; D016875:tau Proteins; D007770:L-Lactate Dehydrogenase; D019791:Guanidine