Evidence for the Involvement of Tiam1 in Axon Formation

Kunda, Patricia; Paglini, Gabriela; Quiroga, Santiago; Kosik, Kenneth S.; Cáceres, Alfredo

doi:10.1523/jneurosci.21-07-02361.2001

Cited by 177 publications

(214 citation statements)

References 41 publications

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“…Among over 30 Rho family GEFs currently known in vertebrates, STEF and Tiam1 are the first GEFs that have been shown to be actually involved in the promotion of neurite growth, although a recent report suggested the involvement of Tiam1 in the polarization of cultured hippocampal neurons (41). Further analyses of STEF and Tiam1, including in vitro and in vivo genetic approaches, would provide important clues as to how extracellular cues ultimately lead to the proper behavior of neurons during the formation of mammalian neuronal network.…”

Section: Functional Significance Of Domains Of the Stef Protein Inmentioning

confidence: 99%

Characterization of STEF, a Guanine Nucleotide Exchange Factor for Rac1, Required for Neurite Growth

Matsuo¹,

Hoshino²,

Yoshizawa³

et al. 2002

Journal of Biological Chemistry

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Accumulating evidence suggests that Rho family GTPases play critical roles in the organization of the nervous system. We previously identified a guanine nucleotide exchange factor of Rac1, STEF (SIF and Tiam 1-like exchange factor), which can induce ruffling membrane in KB cells and is predominantly expressed in the brain during development. Here, we characterize the molecular nature of STEF and its involvement in neurite growth. Deletion analyses revealed distinct roles for individual domains: PHnTSS for membrane association, DH for enzymatic activity, and PHc for promoting catalytic activity. Ectopic expression of STEF in N1E-115 neuroblastoma cells induced neurite-like processes containing F-actin, ␤III tubulin, MAP2, and GAP43 in a Rac1-dependent manner even under the serum-containing neurite-inhibiting conditions. We further found that a PHnTSS STEF fragment specifically inhibited the function of both STEF and Tiam1, a closely related Rac1 guanine nucleotide exchange factor. Suppression of endogenous STEF and Tiam1 activities in N1E-115 cells by ectopically expressed PHnTSS STEF resulted in inhibition of neurite outgrowth in serum-starved conditions, which usually induce neurite formation. Furthermore, these inhibitory effects were rescued by exogenously expressed STEF or Tiam1, suggesting that STEF and Tiam1 are involved in neurite formation through the activation of Rac1 and successive cytoskeletal reorganization of neuronal cells during development.

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Section: Functional Significance Of Domains Of the Stef Protein Inmentioning

confidence: 99%

Characterization of STEF, a Guanine Nucleotide Exchange Factor for Rac1, Required for Neurite Growth

Matsuo¹,

Hoshino²,

Yoshizawa³

et al. 2002

Journal of Biological Chemistry

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“…On the other hand, activation of Rac1 induces neurite elongation. Tiam1, a specific guanine-nucleotide exchange factor (GEF) for Rac1 (Habets et al, 1994), affects neuronal morphology Kunda et al, 2001). Moreover, STEF, another GEF for Rac1, which has highly homologous regions with Tiam1, is also effective in neurite outgrowth (Matsuo et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2

Tanaka

Ohashi

Nakamura

et al. 2004

EMBO J

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Bidirectional signals mediated by Eph receptor tyrosine kinases and their membrane-bound ligands, ephrins, play pivotal roles in the formation of neural networks by induction of both collapse and elongation of neurites. However, the downstream molecular modules to deliver these cues are largely unknown. We report here that the interaction of a Rac1-specific guanine nucleotide-exchanging factor, Tiam1, with ephrin-B1 and EphA2 mediates neurite outgrowth. In cells coexpressing Tiam1 and ephrin-B1, Rac1 is activated by the extracellular stimulation of clustered soluble EphB2 receptors. Similarly, soluble ephrin-A1 activates Rac1 in cells coexpressing Tiam1 and EphA2. Cortical neurons from the E14 mouse embryos and neuroblastoma cells significantly extend neurites when placed on surfaces coated with the extracellular domain of EphB2 or ephrin-A1, which were abolished by the forced expression of the dominant-negative mutant of ephrin-B1 or EphA2. Furthermore, the introduction of a dominant-negative form of Tiam1 also inhibits neurite outgrowth induced by the ephrin-B1 and EphA2 signals. These results indicate that Tiam1 is required for neurite outgrowth induced by both ephrin-B1-mediated reverse signaling and EphA2-mediated forward signaling.

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“…Tiam1, which is widely expressed, is involved in the promotion of invasion in lymphocytes and fibroblasts and adhesion in epithelial cells (13). We noted that Tiam1 is located within growth cones and promotes the formation of axons (14,15). The NMDA receptor controls the growth and morphological changes of dendritic arbors and spines through Tiam1-dependent Rac1 activation (16).…”

mentioning

confidence: 99%

TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and induction of changes in cellular morphology

Miyamoto

Yamauchi

Tanoue

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

135

132

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Small GTPases of the Rho family play key roles in the formation of neuronal axons and dendrites by transducing signals from guidance cues, such as neurotrophins, to the actin cytoskeleton. However, there is little insight into the mechanism by which neurotrophins regulate Rho GTPases. Here, we show the crucial role of the ubiquitous Rac1-specific guanine nucleotide exchange factor, Tiam1 (T lymphoma invasion and metastasis 1), in transducing a neurotrophin-mediated change in cell shape. We demonstrate that BDNF, acting through TrkB, directly binds and specifically activates Tiam1 by phosphorylating Tyr-829, leading to Rac1 activation and lamellipodia formation in Cos-7 cells and increased neurite outgrowth from cortical neurons. A point mutation in Tiam1, Tyr-829 to Phe-829, blocked these BDNF-induced changes in cellular morphology. The findings are evidence of a previously uncharacterized mechanism for the activation of Tiam1 and of a role for this effector in neurotrophin-mediated signal transduction leading to changes in cellular morphology.actin ͉ cortical neuron ͉ neurotrophin ͉ Rho guanine nucleotide exchange factors ͉ Rho GTPases

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Evidence for the Involvement of Tiam1 in Axon Formation

Cited by 177 publications

References 41 publications

Characterization of STEF, a Guanine Nucleotide Exchange Factor for Rac1, Required for Neurite Growth

Characterization of STEF, a Guanine Nucleotide Exchange Factor for Rac1, Required for Neurite Growth

Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2

TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and induction of changes in cellular morphology

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