HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 38, 34755-34759, September 20, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/38/34755    most recent M201201200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by DeTure, M. A. Articles by Purich, D. L. Search for Related Content PubMed PubMed Citation Articles by DeTure, M. A. Articles by Purich, D. L. Social Bookmarking                      What's this?

In Vitro Assembly of Alzheimer-like Filaments
HOW A SMALL CLUSTER OF CHARGED RESIDUES IN Tau AND MAP2 CONTROLS FILAMENT MORPHOLOGY^*

Michael A. DeTure, Luca Di Noto, and Daniel L. Purich

From the Department of Biochemistry & Molecular Biology, and the McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida 32610-0245

Although the microtubule-binding regions (MTBRs) of both Tau and MAP2 can undergo self-assembly into straight filaments (SFs) in vitro, only the Tau MTBR forms paired helical filaments (PHFs). Moreover, Tau appears to be the exclusive building block of the neuropathic filaments observed in Alzheimer's disease and certain frontotemporal dementias (FTDs). Despite significant conservation in the MTBR sequences, there are two persistently different stretches of amino acids (designated here as Module-A and Module-B) between Tau and MAP2 from a number of organisms. To evaluate the role of charged residues in these modules as potential morphology-specifying elements, we used site-directed mutagenesis to replace selected residues within the MAP2 MTBR by residues at corresponding positions in Tau. We then employed electron microscopy to determine the frequency of occurrence of SF and PHF morphology in filaments assembled from these mutant microtubule-binding regions. Our experimental results indicate that a very small number of residues are especially significant determinants of filament morphology; this inference is also supported by the observation that site-directed substitutions of individual Tau residues into MAP2 Module-B likewise result in the formation of PHF-like structures. Because the Module-B in Tau contains two naturally occurring FTD mutations, residues in this region may play a critical role in neuropathic filament assembly.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. D. Mukrasch, M. von Bergen, J. Biernat, D. Fischer, C. Griesinger, E. Mandelkow, and M. Zweckstetter The "Jaws" of the Tau-Microtubule Interaction J. Biol. Chem., April 20, 2007; 282(16): 12230 - 12239. [Abstract] [Full Text] [PDF]

				J. AVILA, J. J. LUCAS, M. PEREZ, and F. HERNANDEZ Role of Tau Protein in Both Physiological and Pathological Conditions Physiol Rev, April 1, 2004; 84(2): 361 - 384. [Abstract] [Full Text] [PDF]