A τ Fragment Containing a Repetitive Sequence Induces Bundling of Actin Filaments

Abstract

Much indirect evidence suggests that the interconnections of actin microfilaments with the microtubule system are mediated by microtubule-associated proteins (MAPs). In this study we provide new data to support the interaction of a specific tubulin-binding domain on tau with actin in vitro. In actin polymerization assays, the synthetic peptide VRSKIGSTENLKHQPGGG, corresponding to the first repetitive sequence of tau protein, increased turbidity at 320 nm in a dose-dependent fashion. A salient feature of the tau peptide-induced assembly process is the formation of a large amount of actin filament bundles, as revealed by electron microscopic analysis. An increase in the tau peptide concentration resulted in a proportional increase in the bundling of actin filaments. It is interesting that a gradual decrease of pH within the range 7.6-4.7 resulted in a higher effect of tau peptide in promoting bundles of actin filaments. A similar pH-dependent effect was observed for tau protein-induced bundling. An analysis of the mechanisms that operate in the peptide induction of actin filament bundles suggests the involvement of electrostatic forces, because the neutralization of epsilon-aminolysyl residues by selective carbamoylation resulted in a complete loss of the peptide induction of actin bundles. The data suggest that a tau repetitive sequence (also found in MAP-2 and MAP-4) containing a common tubulin binding motif may constitute a functional domain on tau for the dynamics of the interconnections between actin filaments and microtubules.

Lamin Dysfunction Mediates Neurodegeneration in Tauopathies

“…In addition to its role as a microtubule-binding protein, tau also binds actin and induces overstabilization and bundling of filamentous actin (F-actin) in tauopathy [25, 26]. Genetically reversing actin overstabilization significantly suppresses tau neurotoxicity [14, 26], demonstrating that overstabilization of F-actin is a causal event in tau-induced neurodegeneration.…”

Interaction of Tau with the Neural Membrane Cortex Is Regulated by Phosphorylation at Sites That Are Modified in Paired Helical Filaments

“…However, it is unlikely that a direct interaction with actin is involved since we never observed a colocalization of tau with actin-rich structures in filopodia of PC12 cells or developing neurons. In addition, actin binding requires the repeat domain, which is also involved in microtubule interaction (48,49), whereas tau binding to the membrane cortex was also observed with a carboxyl-terminally deleted tau fragment lacking the repeats (10). Until now, we NT2-N cells).…”

Tubulin, actin, and tau protein interactions and the study of their macromolecular assemblies

“…MAP-2 was puri®ed as indicated in Vera [1988]. Actin was prepared from chicken muscular tissue [Moraga et al, 1993]. Puri®ed actin preparations were dialyzed in 3 Â Tris buffer pH 8.0 for 2 days at 48C.…”

“…Homologous protein±protein interactions include those of actin polymerization into micro®laments, or tubulin assembly into microtubules, while heterologous interactions include those of actin binding protein with the actin ®lament network, microtubule-associated proteins with microtubules, and with other components of cytoskeletal network [Mandelkow and Mandelkow, 1995;Welch et al, 1997;Mandato et al, 2001]. In this context, since the Porter model on the organization of the cytoplasmic matrix [Ellisman and Porter, 1980], evidence has accumulated on the roles of MAPs in bridging microtubules and actin ®laments in several cell types [Cross et al, 1993;Moraga et al, 1993;Henriquez et al, 1995;Maccioni and Cambiazo, 1995], and also in the interaction of microtubular polymers with intermediate ®laments [Capote and Maccioni, 1998]. The association between microtubules and actin ®laments is critical for cellular morphogenesis.…”