Research article

The proline-rich domain of tau plays a role in interactions with actin

Hai J He^1,2†, Xing S Wang^2†, Rong Pan², Dong L Wang², Ming N Liu¹ and Rong Q He^2*

• * Corresponding author: Rong Q He herq@sun5.ibp.ac.cn

• † Equal contributors

Author Affiliations

¹ State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Key Lab of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, PR China

² Graduate University, Chinese Academy of Sciences, Beijing, PR China

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BMC Cell Biology 2009, 10:81 doi:10.1186/1471-2121-10-81

Published: 8 November 2009

Abstract

Background

The microtubule-associated protein tau is able to interact with actin and serves as a cross-linker between the microtubule and actin networks. The microtubule-binding domain of tau is known to be involved in its interaction with actin. Here, we address the question of whether the other domains of tau also interact with actin.

Results

Several tau truncation and deletion mutants were constructed, namely N-terminal region (tauN), proline-rich domain (tauPRD), microtubule binding domain (tauMTBD) and C-terminal region (tauC) truncation mutants, and microtubule binding domain (tauΔMTBD) and proline-rich domain/microtubule binding domain (tauΔPRD&MTBD) deletion mutants. The proline-rich domain truncation mutant (tauPRD) and the microtubule binding domain deletion mutant (tauΔMTBD) promoted the formation of actin filaments. However, actin assembly was not observed in the presence of the N-terminal and C-terminal truncation mutants. These results indicate that the proline-rich domain is involved in the association of tau with G-actin. Furthermore, results from co-sedimentation, solid phase assays and electron microscopy showed that the proline-rich domain is also capable of binding to F-actin and inducing F-actin bundles. Using solid phase assays to analyze apparent dissociation constants for the binding of tau and its mutants to F-actin resulted in a sequence of affinity for F-actin: tau >> microtubule binding domain > proline-rich domain. Moreover, we observed that the proline-rich domain was able to associate with and bundle F-actin at physiological ionic strength.

Conclusion

The proline-rich domain is a functional structure playing a role in the association of tau with actin. This suggests that the proline-rich domain and the microtubule-binding domain of tau are both involved in binding to and bundling F-actin.