Hsc70 Rapidly Engages Tau after Microtubule Destabilization

• DOI: 10.1074/jbc.m110.113753
• Publication Date: 2010-03-23T02:11:14Z
• Authors: Umesh K. Jinwal; John C. O'Leary; Sergiy I. Borysov; Jeffrey R. Jones; Qingyou Li; John Koren; Jose F. Abisambra; Grant D. Vestal; Lisa Y. Lawson; Amelia G. Johnson; Laura J. Blair; Ying Jin; Yoshinari Miyata; Jason E. Gestwicki; Chad A. Dickey
• Keywords: Microtubule polymerization; Tau protein; Microtubule-associated protein

The microtubule-associated protein Tau plays a crucial role in regulating the dynamic stability of microtubules during neuronal development and synaptic transmission. In group neurodegenerative diseases, such as Alzheimer disease other tauopathies, conformational changes are associated with initial stages pathology. Folding into MC1 conformation, where amino acids at residues 7–9 interact 312–342, is one earliest pathological alterations disease. mechanism this change subsequent effect on function association to largely unknown. Recent work by our others suggests that members Hsp70 family play significant regulation. Our new findings suggest heat shock cognate (Hsc) 70 facilitates Tau-mediated microtubule polymerization. Hsc70 was rapidly enhanced following treatment microtubule-destabilizing agents. fate released from found be dependent ATPase activity Hsc70. Microtubule destabilization also increased folded conformation Tau. An vitro assay formation However, hyperphosphorylating environment, abrogated, but binding enhanced. Thus, under normal circumstances, may protective facilitated diseased preserve more unstructured state, perhaps facilitating its pathogenicity.