Title

Peroxynitrite-mediated tau modifications stabilize preformed filaments and destabilize microtubules through distinct mechanisms.

Journal

Biochemistry

Volume

45

Issue

None

Pages

4314-26

Date

2006-04-04

Authors

Berry RW | Binder LI | Lukas TJ | Reynolds MR

During Abeta-associated inflammation, reactive nitrogen and oxygen species are generated that can cause neuronal dysfunction and death (34-37). Prevalent among these species is peroxynitrite (ONOO-)

Previously, we showed that peroxynitrite (ONOO-) induces the oxidative 3,3¢- dityrosine (3,3¢-DT) cross-linking and site-selective nitration of tau monomers [Reynolds et al. (2005)

Select nitration of residues Tyr18, Tyr29, Tyr197, and Tyr394, events known to stabilize the pathological Alz-50 conformation inhibits the ability of monomeric tau to promote tubulin assembly, effect specific for the 3-NT modification, as mutant tau proteins pseudophosphorylated at each Tyr residue are fully competent to stabilize MTs, suggesting that ONOO(-)-mediated modifications stabilize tau filaments via 3,3'-DT bonding and destabilize MTs by site-selective nitration of tau monomers.

Further, select nitration of residues Tyr18, Tyr29, Tyr197, and Tyr394, events known to stabilize the pathological Alz-50 conformation [Reynolds et al. (2005) Biochemistry 44, 13997-14009], inhibits the ability of monomeric tau to promote tubulin assembly.

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