Microtubule-mediated Src Tyrosine Kinase Trafficking in Neuronal Growth Cones

Wu, Bingbing; Decourt, Boris; Zabidi, Muhammad A.; Wuethrich, Levi T.; Kim, William H.; Zhou, Zhigang; MacIsaac, Keira; Suter, Daniel M.

doi:10.1091/mbc.e08-06-0603

Cited by 27 publications

(53 citation statements)

References 64 publications

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“…Thus, the dynamic positioning of PTP1B at the peripheral region of growth cones may contribute to the activation of Src. Using a membrane-targeted FRET sensor, we found that Src is active at the growth cone and filopodia, in agreement with previous immunodetection of phospho-active forms of Src (Robles et al, 2005;Wu et al, 2008). Interestingly, overexpression of PTP1B increased the FRET signal in the peripheral region and filopodia.…”

Section: Regulation Of Filopodial Dynamics and Src Activation By Ptp1bsupporting

confidence: 90%

“…Recent work suggests that Src activity is required for filopodia initiation, extension, and dynamics (Robles et al, 2005;Wu et al, 2008). In addition, we and others have shown that Src activity is promoted by PTP1B in nonneuronal cells Bjorge et al, 2000).…”

Section: Ptp1b Regulates Growth Cone Dynamics and Src Activitymentioning

confidence: 67%

“…The protein tyrosine kinase Src localizes in growth cones where appears to regulate the formation and extension of filopodia (Robles et al, 2005;Wu et al, 2008). PTP1B dephosphorylates the C-terminus regulatory site of c-Src leading to its activation Bjorge et al, 2000).…”

Section: Regulation Of Filopodial Dynamics and Src Activation By Ptp1bmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…This process would facilitate the translocation of vesicular and other membranous compartments to contact sites (Waterman-Storer et al, 2000;Ligon and Holzbaur, 2007; Shaw et al, 2007;Spiliotis et al, 2008). Some degree of microtubule dynamics, however, seems to be required for events induced by target interactions of growth cones, including morphological changes, the assembly of an actin scaffold, and the activation of Src tyrosine kinases (Suter et al, 2004;Wu et al, 2008).The endoplasmic reticulum (ER) is a continuous membranous compartment that essentially reaches every part of the cell (Vedrenne and Hauri, 2006). In growth cones the ER is prominent in the central domain and extends fingerlike processes dynamically to the peripheral region, which frequently coalign with microtubules (Dailey and Bridgman, 1989).…”

mentioning

confidence: 99%

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Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

Fuentes

Arregui

2009

MBoC

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PTP1B is an ER-bound protein tyrosine phosphatase implied in the regulation of cell adhesion. Here we investigated mechanisms involved in the positioning and dynamics of PTP1B in axonal growth cones and evaluated the role of this enzyme in axons. In growth cones, PTP1B consistently localizes in the central domain, and occasionally at the peripheral region and filopodia. Live imaging of GFP-PTP1B reveals dynamic excursions of fingerlike processes within the peripheral region and filopodia. PTP1B and GFP-PTP1B colocalize with ER markers and coalign with microtubules at the peripheral region and redistribute to the base of the growth cone after treatment with nocodazole, a condition that is reversible. Growth cone contact with cellular targets is accompanied by invasion of PTP1B and stable microtubules in the peripheral region aligned with the contact axis. Functional impairment of PTP1B causes retardation of axon elongation, as well as reduction of growth cone filopodia lifetime and Src activity. Our results highlight the role of microtubules and cell contacts in the positioning of ER-bound PTP1B to the peripheral region of growth cones, which may be required for the positive role of PTP1B in axon elongation, filopodia stabilization, and Src activity. INTRODUCTIONProper discrimination and response to extracellular signals by axonal growth cones are crucial for the wiring of the nervous system. The sensing activity is performed by receptors in the plasma membrane of growth cones, from which cell adhesion receptors represent a major category. In part, information relied by these receptors regulates the behavior of the cytoskeleton and other macromolecular complexes (Suter and Forscher, 2000;Huber et al., 2003). Growth cone responses vary, but depend on the dynamic properties of microfilaments and microtubules. Microtubules explore dynamically the periphery of growth cones and occasionally penetrate into filopodia (Gordon-Weeks, 1991;Tanaka and Kirschner, 1991;Schaefer et al., 2002;Brown and Bridgman, 2003;Schober et al., 2007). It was early proposed that a subset of exploratory microtubules become selectively stabilized in response to extracellular cues (Kirschner and Mitchison, 1986;Mitchison and Kirschner, 1988). Indeed, imaging of Ti1 pioneer neurons in live grasshopper embryonic limb buds shows the selective invasion of microtubules toward growth cone branches that contact guidepost cells (Sabry et al., 1991). Furthermore, studies in bag cell neurons of Aplysia show that microtubules quickly invade regions of contact between growth cone filopodia and neighboring cells or beads coated with ApCAM (Lin and Forscher, 1993;Suter et al., 2004). This process would facilitate the translocation of vesicular and other membranous compartments to contact sites (Waterman-Storer et al., 2000;Ligon and Holzbaur, 2007; Shaw et al., 2007;Spiliotis et al., 2008). Some degree of microtubule dynamics, however, seems to be required for events induced by target interactions of growth cones, including morphological changes, the assem...

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Section: Regulation Of Filopodial Dynamics and Src Activation By Ptp1bsupporting

confidence: 90%

Section: Ptp1b Regulates Growth Cone Dynamics and Src Activitymentioning

confidence: 67%

Section: Regulation Of Filopodial Dynamics and Src Activation By Ptp1bmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

Fuentes

Arregui

2009

MBoC

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Cytoskeletal architecture regulates cyclooxygenase‐2 in human endothelial cells: Autocrine modulation by prostacyclin

Eligini

Songia

Cavalca

et al. 2012

Journal Cellular Physiology

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Endothelium is a highly dynamic tissue that controls vascular homeostasis. This requires constant rearrangements of the shape or function of endothelial cells that cannot set aside the role of the cytoskeleton. The aim of this study was to determine the mechanisms by means of which cytoskeletal alterations induce cyclooxygenase-2 (Cox-2) expression in human endothelial cells using compounds that interfere with microtubule or actin architecture. Microtubule disruption by nocodazole markedly increased Cox-2 expression and activity, and provoked paracellular gap formation, a cardinal feature of endothelial barrier dysfunction. The Cox-2 metabolite prostacyclin down-regulated Cox-2 through an autocrine receptor-mediated mechanism, and partially prevented the disassembly of endothelial monolayers. There was also an interaction between microtubules and actin filaments in nocodazole-induced Cox-2 expression. Nocodazole provoked the dissolution of the F-actin cortical ring and stress fiber formation, increased actin glutathionylation, and concomitantly lowered intracellular levels of reduced glutathione. The restoration of glutathione levels by N-acetylcysteine opposed Cox-2 expression and preserved the integrity of endothelial monolayers. Among the signaling pathways connecting microtubule disruption with Cox-2 up-regulation, crucial roles are played by Src family kinase activation, serine/threonine phosphatase 2A inhibition, and the phosphorylation of mitogen activated protein kinase p38. Our findings provide a mechanistic insight into the observation that Cox-2 is induced in endothelial cells under cytoskeleton-perturbing conditions such as those occurring in the presence of atherogenic/inflammatory stimuli and oxidative stress. In this scenario, Cox-2 up-regulation by endothelia exposed to noxious conditions can be considered protective of the vasodilatory and anti-thrombotic properties of the vessel wall.

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Cortactin colocalizes with filopodial actin and accumulates at IgCAM adhesion sites in Aplysia growth cones

Decourt

Munnamalai

Lee

et al. 2008

J of Neuroscience Research

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Both IgCAMs and the actin cytoskeleton play critical roles in neuronal growth cone motility and guidance. However, it is unclear how IgCAM receptors transduce signals from the plasma membrane to induce actin remodeling. Previous studies have shown that local clustering and immobilization of apCAM, the Aplysia homolog of NCAM, induces Src kinase activity and F-actin polymerization in the peripheral domain of cultured Aplysia bag cell growth cones. Therefore, we wanted to test whether the Src kinase substrate and actin regulator cortactin could be a molecular link between Src activity and actin assembly during apCAM-mediated growth cone guidance. Here, we cloned Aplysia cortactin and showed that it is abundant in the nervous system. Immunostaining of growth cones revealed a strong colocalization of cortactin with F-actin in filopodial bundles and at the leading edge of lamellipodia. Perturbation of the cytoskeleton indicated that cortactin distribution largely depends on actin filaments. Furthermore, active Src colocalized with cortactin in regions of actin assembly, including leading edge and filopodia tips. Finally, we observed that cortactin, like F-actin, localizes to apCAM adhesion sites mediating growth cone guidance. Altogether, these data suggest that cortactin is a mediator of IgCAM-triggered actin assembly in the growth cone and involved in motility and guidance.

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Microtubule-mediated Src Tyrosine Kinase Trafficking in Neuronal Growth Cones

Cited by 27 publications

References 64 publications

Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

Microtubule and Cell Contact Dependency of ER-bound PTP1B Localization in Growth Cones

Cytoskeletal architecture regulates cyclooxygenase‐2 in human endothelial cells: Autocrine modulation by prostacyclin

Cortactin colocalizes with filopodial actin and accumulates at IgCAM adhesion sites in Aplysia growth cones

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