Rac interacts with Abi-1 and WAVE2 to promote an Arp2/3-dependent actin recruitment during chlamydial invasion

Carabeo, Rey A.; Dooley, Cheryl A.; Grieshaber, Scott S.; Hackstadt, Ted

doi:10.1111/j.1462-5822.2007.00958.x

Cited by 60 publications

(88 citation statements)

References 67 publications

(166 reference statements)

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“…In the EB, the type III secretion system (a multiprotein needlelike delivery system) (reviewed in Beeckman and Vanrompay 2010), is poised for immediate discharge of effectors on contact with the host cell. At least one early secreted effector, TARP, contributes to bacterial internalization by its ability to directly nucleate actin polymerization through a WH2 actin-binding domain mimic (Jewett et al 2006) and by recruiting the guanine nucleotide exchange factors (GEFs) Sos1 and Vav2, which activate Rac1 and signal to the actin machinery (Carabeo et al 2007;Lane et al 2008). This latter mechanism is only relevant in chlamydial species inwhich the polymorphic TARP gene (Clifton et al 2005) can be targeted for tyrosine phosphorylation by Abl, Src, and Syk kinases (Elwell et al 2008;Jewett et al 2008;Lane et al 2008;Mehlitz et al 2008Mehlitz et al , 2010.…”

Section: Mechanisms Of Chlamydia Invasion Of Epithelial Cellsmentioning

confidence: 99%

“…Rac1 is required for C. trachomatis entry (Carabeo et al 2004), whereas Cdc42 and Arf6 are also required for Chlamydophila caviae internalization Balana et al 2005). Rac1 activation results in the recruitment of the actin regulators WAVE2, Abi-1, and Arp2/ 3, which are necessary for C. trachomatisinduced actin reorganization (Carabeo et al 2007). Both chlamydial and host proteins may function synergistically to promote invasion.…”

Section: Mechanisms Of Chlamydia Invasion Of Epithelial Cellsmentioning

confidence: 99%

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Chlamydial Intracellular Survival Strategies

Bastidas

Elwell

Engel

et al. 2013

Cold Spring Harbor Perspectives in Medicine

195

191

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Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen and the causative agent of blinding trachoma. Although Chlamydia is protected from humoral immune responses by residing within remodeled intracellular vacuoles, it still must contend with multilayered intracellular innate immune defenses deployed by its host while scavenging for nutrients. Here we provide an overview of Chlamydia biology and highlight recent findings detailing how this vacuole-bound pathogen manipulates host -cellular functions to invade host cells and maintain a replicative niche.

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Section: Mechanisms Of Chlamydia Invasion Of Epithelial Cellsmentioning

confidence: 99%

Section: Mechanisms Of Chlamydia Invasion Of Epithelial Cellsmentioning

confidence: 99%

Chlamydial Intracellular Survival Strategies

Bastidas

Elwell

Engel

et al. 2013

Cold Spring Harbor Perspectives in Medicine

195

191

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“…Activation of Rac has been demonstrated to play an important role in processes induced by growth factor (17) and integrin (18). During cell migration, Rac1 translocates to the plasma membrane (19), interacts with WAVE via an adaptor protein, the insulin receptor substrate Irsp53, and then stimulates Arp2/3-mediated actin polymerization (20).…”

Section: Introductionmentioning

confidence: 99%

Vasodilator-stimulated phosphoprotein regulates osteosarcoma cell migration

Wei

et al. 2011

Oncol Rep

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Abstract. Vasodilator-stimulated phosphoprotein (VASP) has been reported to play an important role in the process of cell migration and tumor metastasis. However, to date, no study has examined VASP expression and its function in osteocarcoma cells. In this study, we analyzed the effect of VASP on osteosarcoma cell migration and the signal transduction pathways involved. We used two osteosarcoma cell strains (Mg-63 and Saos-2 cells) with different metastatic potential. Silencing of VASP gene expression was carried out using RNA interference in these cells. Knockdown of expression at the transcriptional or translational level was determined by RT-PCR or Western blot analysis, respectively. The metastatic potential of the tumor cells was determined by a wound healing migration assay. VASP mRNA expression was also determined in 30 human osteosarcoma samples. Furthermore, Rac1 was determined as a regulator of VASP function. RT-PCR and Western blotting showed that Mg-63 cells had a significantly higher VASP expression at both the transcriptional and translational levels compared to Saos-2 cells. The wound healing assay revealed that Mg-63 cells had more migratory potential compared to Saos-2 cells. The effect was found to be reversible when VASP was knocked down by siRNA in Mg-63 cells. Specimens from human patients with metastases had higher VASP expression compared to specimens of patients without metastases. Knockdown of Rac1 resulted in inhibition of VASP expression in sarcoma cells. These results suggest that VASP protein regulates osteosarcoma cell migration and metastasis. Rac1 and VASP interaction may be a potential target for osteosarcoma treatment. IntroductionOsteosarcoma is the most prevalent primary malignant bone tumor in children and young adults. Although the life expectancy of osteosarcoma patients has been prolonged due to improvement of neoadjuvant chemotherapy and surgical resection during the past three decades, the long-term survival and quality of life is still unsatisfactory. Poor outcome of osteosarcoma is mainly caused by metastatic disease, and previous studies have demonstrated that more than 30% of patients already display distant metastasis without clinical detectable signs at the time of diagnosis (1,2).Vasodilator-stimulated phosphoprotein (VASP), a member of the Ena/VASP family, has been implicated in regulating key cellular functions, such as shape change, adhesion and migration, which is mainly due to its ability to modify dynamic action cytoskeleton (3). In addition to its role in normal cell growth (4,5), embryonic development (6) and homeostasis (7), VASP plays an essential role in many diseases, such as cancer metastasis (8,9), thrombosis (10), arteriosclerosis (11) and nephritis (12).Expression of VASP has been reported to be dysregulated in several types of malignancies and is relevant to tumor metastasis. For example, its level was found to be significantly increased in lung adenocarcinomas and gastric carcinomas compared to normal tissue, and this increase was correlated wit...

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“…35 Subsequently, Rac1 recruits WAVE2 and Abl interactor 1 (Abi-1), leading to actin-related protein (Arp2/3) complex activation and actin recruitment and polymerization at the bacterial binding site. 36 It has been proposed that a synergistic action between both bacterial and host cell proteins promotes invasion. In addition, other host tyrosine kinases, such as platelet derived growth factor receptor (PDFGR) and feline Gardner-Rasheed sarcoma viral oncogene homolog (FGR), are phosphorylated upon infection and recruited to the Chlamydia attachment site.…”

mentioning

confidence: 99%