Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2

Tanaka, Masamitsu; Ohashi, Riuko; Nakamura, Ritsuko; Shinmura, Kazuya; Kamo, Takaharu; Sakai, Ryuichi; Sugimura, Haruhiko

doi:10.1038/sj.emboj.7600128

Cited by 88 publications

(78 citation statements)

References 34 publications

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“…Still life (SIF) and Trio in Drosophila, Unc-73 in Caenorhabditis elegans, and Kalirins in mammals were shown to take part in synaptogenesis, neuritogenesis, axonal pathfinding, or dendritic morphogenesis (Sone et al, 1997Steven et al, 1998;Awasaki et al, 2000;Lin and Greenberg, 2000;Penzes et al, 2003). Observations from our group and others also suggested that STEF (SIF and Tiam1-like exchange factor) and Tiam1 (Tcell lymphoma invasion and metastasis 1), both orthologs of Drosophila SIF, are involved in neuritogenesis as well as neuronal migration Kunda et al, 2001;Matsuo et al, 2002;Kawauchi et al, 2003;Matsuo et al, 2003;Tanaka et al, 2004).…”

Section: Introductionmentioning

confidence: 81%

Involvement of a Rac Activator, P-Rex1, in Neurotrophin-Derived Signaling and Neuronal Migration

Yoshizawa¹,

Kawauchi²,

Sone³

et al. 2005

J. Neurosci.

106

114

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Rho-family GTPases play key roles in regulating cytoskeletal reorganization, contributing to many aspects of nervous system development. Their activities are known to be regulated by guanine nucleotide exchange factors (GEFs), in response to various extracellular cues. P-Rex1, a GEF for Rac, has been mainly investigated in neutrophils, in which this molecule contributes to reactive oxygen species formation. However, its role in the nervous system is essentially unknown. Here we describe the expression profile and a physiological function of P-Rex1 in nervous system development. In situ hybridization revealed that P-Rex1 is dynamically expressed in a variety of cells in the developing mouse brain, including some cortical and DRG neurons. In migrating neurons in the intermediate zone, P-Rex1 protein was found to localize in the leading process and adjacent cytoplasmic region. When transfected in pheochromocytoma PC12 cells, P-Rex1 can be activated by NGF, causing an increase in GTP-bound Rac1 and cell motility. Deletion analyses suggested roles for distinct domains of this molecule. Experiments using a P-Rex1 mutant lacking the Dbl-homology domain, a dominant-negative-like form, and small interfering RNA showed that endogenous P-Rex1 was involved in cell migration of PC12 cells and primary cultured neurons from the embryonic day 14 cerebral cortices, induced by extracellular stimuli (NGF, BDNF, and epidermal growth factor). Furthermore, in utero electroporation of the mutant protein into the embryonic cerebral cortex perturbed radial neuronal migration. These findings suggest that P-Rex1, which is expressed in a variety of cell types, is activated by extracellular cues such as neurotrophins and contributes to neuronal migration in the developing nervous system.

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Section: Introductionmentioning

confidence: 81%

Involvement of a Rac Activator, P-Rex1, in Neurotrophin-Derived Signaling and Neuronal Migration

Yoshizawa¹,

Kawauchi²,

Sone³

et al. 2005

J. Neurosci.

106

114

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“…Because EphA4/Fc binds and masks ephrin ligands present on the surface of astrocytes, direct astrocytic contacts no longer initiate signaling events within the dendritic cytoplasm. Ephrin-Eph interaction activates guanine-nucleotide exchange factors, such as Ephexin (Shamah et al, 2001) and Tiam1 (Tanaka et al, 2004), and leads to reorganization of the actin cytoskeleton through modulation of Rho GTPases (Tashiro and Yuste, 2004;Redmond and Ghosh, 2001). Because Ephexin activity in the growth cone has been shown to promote the growth cone collapse through the enhancement of RhoA activation (Shamah et al, 2001), similar structural stabilization may play a role in maintenance of contacts between dendritic protrusions and astrocytes.…”

Section: Discussionmentioning

confidence: 99%

Direct Astrocytic Contacts Regulate Local Maturation of Dendritic Spines

Nishida¹,

Okabe²

2007

J. Neurosci.

229

230

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Astrocytes contribute on both development and function of synapses, but it remains unclear whether direct astrocytic contacts regulate development of individual synapses. Two-photon time-lapse imaging of astrocytic and dendritic protrusive activity revealed the correlation of astrocytic contacts with both lifetime and morphological maturation of dendritic protrusions. Astrocytic motility was essential in maturation of spines, because its suppression by manipulating Rac1-dependent signaling in astrocytes resulted in induction of longer, filopodia-like dendritic protrusions. Manipulation of ephrin/Eph-dependent neuron–astrocyte signaling suggested involvement of this signaling pathway in astrocyte-dependent stabilization of newly generated dendritic protrusions. Our data support a model in which astrocytic protrusive activity in development acts as a key local regulator for stabilization of individual dendritic protrusions and subsequent maturation into spines.

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“…In nonlymphoid cells, ephrin-B1 is known to regulate cell behavior through small GTPases of the Rho and Ras families (19,28,29,65); however, the molecular mechanism allowing ephrin-B1 to control these molecules has not been addressed. Because ephrin-B1 has also been shown to be able to attract GRIP proteins through their PDZ domains into the lipid rafts (13), we examined if ephrin-B1 may also control the association of small GTPases with raft microdomains.…”

Section: Ephrin-b1 Is Consistently Expressed By Pediatric T-all Cellsmentioning

confidence: 99%

“…At a cellular level, ephrin-B activity results in cytoskeletal rearrangements (11), inhibition of chemokine-induced migration (15), and generation of adhesive (27)(28)(29) or repulsive responses (11,(19)(20)(21)(30)(31)(32)(33)(34)(35).…”

Section: Introductionmentioning

confidence: 99%

In Human Leukemia Cells Ephrin-B–Induced Invasive Activity Is Supported by Lck and Is Associated with Reassembling of Lipid Raft Signaling Complexes

Jiang

Freywald

Webster

et al. 2008

Molecular Cancer Research

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Proteins of the ephrin-B group operate in nonlymphoid cells through the control of their migration and attachment, and are crucial for the development of the vascular, lymphatic, and nervous systems. Ephrin-B activity is deregulated in various nonlymphoid malignancies; however, their precise role in cancer has only started to be addressed. We show here that ephrin-B1, a member of the ephrin-B group, is expressed in pediatric T-cell leukemias, including leukemia cell line Jurkat. Treatment of Jurkat cells with ephrin-Bstimulating EphB3 enhances ephrin-B1 phosphorylation and induces its relocalization into lipid rafts. These events are mediated by the T lineage -specific kinase, Lck, as ephrin-B1 phosphorylation and lipid raft association are blocked in the Lck-deficient clone of Jurkat, JCAM1.6. Ephrin-B1 also induces colocalization of the CrkL and Rac1 cytoskeleton regulators and initiates in leukemic cells a strong repulsive response. The absence of Lck blocks ephrin-B1 -induced signaling and repulsion, confirming the essential role for Lck in ephrin-B1 -mediated responses. This shows a new role for ephrin-B1 in the regulation of leukemic cells through the Lck-dependent Rac1 colocalization with its signaling partner, CrkL, in lipid rafts. In agreement with its repulsive action, ephrin-B1 seems to support metastatic properties of leukemic cells, as suppression of ephrin-B1 signaling inhibits their invasiveness. Because ephrin-B1 -activating EphB proteins are ubiquitously expressed, our findings suggest that ephrin-B1 is likely to play an important role in the regulation of malignant T lymphocytes through the control of lipid-raftassociated signaling, adhesion, and invasive activity, and therefore may represent a novel target for cancer treatment. (Mol Cancer Res 2008;6(2):291 -305)

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Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2

Cited by 88 publications

References 34 publications

Involvement of a Rac Activator, P-Rex1, in Neurotrophin-Derived Signaling and Neuronal Migration

Involvement of a Rac Activator, P-Rex1, in Neurotrophin-Derived Signaling and Neuronal Migration

Direct Astrocytic Contacts Regulate Local Maturation of Dendritic Spines

In Human Leukemia Cells Ephrin-B–Induced Invasive Activity Is Supported by Lck and Is Associated with Reassembling of Lipid Raft Signaling Complexes

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