Tau associates with actin in differentiating PC12 cells

Yu, Jiang Zhou; Rasenick, Mark M.

doi:10.1096/fj.05-5206com

Cited by 57 publications

(44 citation statements)

References 42 publications

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“…In agreement, local inactivation of SFKs also resulted in growth cone collapse (Robles et al, 2005) and growth cones expressing dominant negative Rac1 had reduced lamellipodial protrusions (Woo and Gomez, 2006). Most recently, in PC12 cells, tau has been localized to lamellipodia-like structures in an NGF-dependent manner, where it associated with actin (Yu and Rasenick, 2006). In addition, the N-terminus was required for the NGF-dependent aspect of the localization.…”

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confidence: 57%

Tau impacts on growth-factor-stimulated actin remodeling

Sharma

Litersky

Bhaskar

et al. 2007

Journal of Cell Science

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The microtubule-associated protein tau interacts with the SH3 domain of non-receptor Src family protein tyrosine kinases. A potential consequence of the SH3 interaction is the upregulation of tyrosine kinase activity. Here we investigated the activation of Src or Fyn by tau, both in vitro and in vivo. Tau increased the kinase activity in in vitro assays and in transfected COS7 cells. In plateletderived growth factor (PDGF)-stimulated fibroblasts, tau appeared to prime Src for activation following PDGF stimulation, as reflected by changes in Src-mediated actin rearrangements. In addition, while fibroblasts normally recovered actin stress fibers by 5-7 hours after PDGF stimulation, tau-expressing cells showed sustained actin breakdown. Microtubule association by tau was not required for the observed changes in actin morphology. Inhibition of Src kinases or a mutant deficient in Src interaction reduced the effects, implicating Src family protein tyrosine kinases as a mediator of the effects of tau on actin rearrangements. Our results provide evidence that the interaction of tau with Src upregulates tyrosine kinase activity and that this interaction allows tau to impact on growth-factor-induced actin remodeling. Journal of Cell Science Tau impacts on actin remodeling Results Tau affects SFK activityWe have previously shown through in vitro binding assays that human tau interacted with the SH3 domain of Fyn and Src (Bhaskar et al., 2005;Lee et al., 1998). Based on the crystal structure of Src, SH3 ligands are thought to 'unclamp' an inactive form of Src, enhancing its activation (Xu et al., 1999;Xu et al., 1997). Our first indication that tau might function in this manner came from experiments initially performed to examine the ability of tyrosine-phosphorylated tau to associate with microtubules. Purified tau and Fyn were incubated in an in vitro kinase reaction to first generate tyrosinephosphorylated tau. The reaction was then added to taxolstabilized microtubules. Upon examining the microtubule pellet for tyrosine-phosphorylated tau, we discovered that the taxol-stabilized tubulin was also tyrosine phosphorylated, presumably by the Fyn that had been carried over from the kinase reaction. Moreover, although Fyn alone was capable of phosphorylating taxol-stabilized microtubules, the presence of tau greatly enhanced the phosphorylation (Fig. 1A, compare lanes 4 and 8).However, because tau binds to microtubules, a possible explanation for the enhanced tubulin phosphorylation was that tau was simply bringing Fyn to the microtubules and facilitating tubulin phosphorylation without affecting Fyn activity. This would predict that a fragment of tau lacking microtubule-binding activity would be incapable of enhancing the phosphorylation. We therefore tested an N-terminal fragment of tau that binds to Fyn SH3 but lacks the microtubule-binding repeats [amino acids 1-184 (Lee et al., 1998)]. By using the same protocol in which the tau fragment was incubated with Fyn and then added to taxol-stabilized microtubules, we found ...

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confidence: 57%

Tau impacts on growth-factor-stimulated actin remodeling

Sharma

Litersky

Bhaskar

et al. 2007

Journal of Cell Science

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“…Tau can also bind to and bundle actin filaments (Fulga et al, 2007; He et al, 2009; Kotani et al, 1985), activities mediated primarily by its MBD (Farias et al, 2002; Yu and Rasenick, 2006) and assisted by the adjacent proline-rich domain (He et al, 2009) (Figure 1). It is possible that tau connects microtubule and actin filament networks (Farias et al, 2002).…”

Section: Evidence For Multiple Functions Of Taumentioning

confidence: 99%

“…Thus, increased levels of tau may enhance NGF function, whereas the N-terminus of tau may impair NGF signaling, possibly by a dominant-negative mechanism. Enhancement of NGF signaling by tau may involve increased association of tau with actin filaments, which occurs after stimulation with NGF and is mainly mediated by the MBD (Yu and Rasenick, 2006) rather than the N-terminus. In PC12 cells, tau facilitates signaling through receptors for NGF and epidermal growth factor (EGF), thereby increasing activity in the mitogen-activated protein kinase (MAPK) pathway (Leugers and Lee, 2010).…”

Section: Evidence For Multiple Functions Of Taumentioning

confidence: 99%

The Many Faces of Tau

Morris

Maeda

Vossel

et al. 2011

Neuron

769

699

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“…Sub-portions of tau co-immunoprecipitated with actin filaments have been found in various cell types [4]. As described by Yu and colleagues [13], under NGF stimulation, tau is distributed at the ends of cellular extensions, where it associates with actin in a microtubule-independent manner in PC12 cells. Moreover, Fluga and co-workers [14] have provided evidence that tau induces changes in the organization and stability of neuronal actin filaments, which in turn contributes to Alzheimer's-like neurodegeneration in Drosophila and mouse model systems.…”

Section: Introductionmentioning

confidence: 98%

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

et al. 2009

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BackgroundThe 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.ResultsSeveral 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.ConclusionThe 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.

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Tau associates with actin in differentiating PC12 cells

Cited by 57 publications

References 42 publications

Tau impacts on growth-factor-stimulated actin remodeling

Tau impacts on growth-factor-stimulated actin remodeling

The Many Faces of Tau

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

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