Ena/VASP Proteins: Regulators of the Actin Cytoskeleton and Cell Migration

Krause, Matthias; Dent, Erik W.; Bear, James E.; Loureiro, Joseph; Gertler, Frank B.

doi:10.1146/annurev.cellbio.19.050103.103356

Cited by 604 publications

(631 citation statements)

References 106 publications

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“…Molecular functions of VASP are regulated by several phosphorylation sites [14,15]. We found that UDP induced the transient phosphorylation of VASP at Ser157.…”

Section: Udp Induced the Phosphorylation And Translocation Of Vaspmentioning

confidence: 82%

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Kataoka¹,

Koga²,

Uesugi³

et al. 2011

Purinergic Signalling

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Microglia are major immunocompetent cells in the central nervous system and retain highly dynamic motility. The processes which allow these cells to move, such as chemotaxis and phagocytosis, are considered part of their functions and are closely related to purinergic signaling. Previously, we reported that the activation of the P2Y 6 receptor by UDP stimulation in microglia evoked dynamic cell motility which enhanced their phagocytic capacity, as reported by Koizumi et al. (Nature 446 (7139):1091-1095. These responses require actin cytoskeletal rearrangement, which is seen after UDP stimulation. However, the intracellular signaling pathway has not been defined. In this study, we found that UDP in rat primary microglia rapidly induced the transient phosphorylation at Ser157 of vasodilator-stimulated phosphoprotein (VASP). VASP, one of actin binding protein, accumulated at the plasma membrane where filamentous (F)-actin aggregated in a time-dependent manner. The phosphorylation of VASP was suppressed by inhibition of PKC. UDP-induced local actin aggregations were also abrogated by PKC inhibitors. The Rho inhibitor CT04 and the expression of p115-RGS, which suppresses G 12/13 signaling, attenuated UDP-induced phosphorylation of VASP and actin aggregation. These results indicate that PKC-and Rho-dependent phosphorylation of VASP is involved in UDP-induced actin aggregation of microglia.

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“…Molecular functions of VASP are regulated by several phosphorylation sites [14,15]. We found that UDP induced the transient phosphorylation of VASP at Ser157.…”

Section: Udp Induced the Phosphorylation And Translocation Of Vaspmentioning

confidence: 82%

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Kataoka¹,

Koga²,

Uesugi³

et al. 2011

Purinergic Signalling

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“…EVL, hsa-miR-342 and p16/CDKN2A RNA levels were measured using TaqMan-based qRT-PCR assays. cytoskeleton remodeling and cell polarity such as axon guidance and lamellipodial and filopodial dynamics in migrating cells (Krause et al, 2003). It is possible that EVL could function as a tumor suppressor through effects on cell shape or motility.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer

et al. 2008

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MicroRNAs are small, non-coding RNAs that influence gene regulatory networks by post-transcriptional regulation of specific messenger RNA targets. MicroRNA expression is dysregulated in human malignancies, frequently leading to loss of expression of certain microRNAs. We report that expression of hsa-miR-342, a microRNA encoded in an intron of the gene EVL, is commonly suppressed in human colorectal cancer. The expression of hsa-miR-342 is coordinated with that of EVL and our results indicate that the mechanism of silencing is CpG island methylation upstream of EVL. We found methylation at the EVL/hsa-miR-342 locus in 86% of colorectal adenocarcinomas and in 67% of adenomas, indicating that it is an early event in colorectal carcinogenesis. In addition, we observed a higher frequency of methylation (56%) in histologically normal colorectal mucosa from individuals with concurrent cancer compared to mucosa from individuals without colorectal cancer (12%), suggesting the existence of a 'field defect' involving methylated EVL/hsa-miR-342. Furthermore, reconstitution of hsa-miR-342 in the colorectal cancer cell line HT-29 induced apoptosis, suggesting that this microRNA could function as a proapoptotic tumor suppressor. In aggregate, these results support a novel mechanism for silencing intronic microRNAs in cancer by epigenetic alterations of cognate host genes.

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“…Members of the Ena/VASP family are highly conserved proteins implicated in actin-dependent dynamic cellular processes (Krause et al, 2003). The vertebrate members of the Ena/VASP family are VASP (vasodilator-stimulated phosphoprotein), Mena (mammalian-enabled) and Ena-VASP-like (EVL).…”

Section: Introductionmentioning

confidence: 99%

“…The vertebrate members of the Ena/VASP family are VASP (vasodilator-stimulated phosphoprotein), Mena (mammalian-enabled) and Ena-VASP-like (EVL). Ena/VASP proteins localize to sites of active actin rearrangements, including focal adhesions, the leading edge of lamellipodia, the tips of filopodia, cell-to-cell contacts and stress fibres, where they contribute to actin assembly and cell motility (Krause et al, 2003). They promote actin filament elongation by delaying binding of capping proteins and by recruiting profilin/G-actin to sites of actin polymerization (Bear & Gertler, 2009;Breitsprecher et al, 2011;Hansen & Mullins, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery

2015

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Shigella spp. are intracellular bacterial pathogens that cause diarrhoeal disease in humans. Shigella utilize the host actin cytoskeleton to enter cells, move through the cytoplasm of cells and pass into adjacent cells. Ena/VASP family proteins are highly conserved proteins that participate in actin-dependent dynamic cellular processes. We tested whether Ena/VASP family members VASP (vasodilator-stimulated phosphoprotein), Mena (mammalian-enabled) or EVL (Ena-VASP-like) contribute to Shigella flexneri spread through cell monolayers. VASP and EVL restricted cell-to-cell spread without significantly altering actin-based motility, whereas Mena had no effect on these processes. Phosphorylation of VASP on Ser153, Ser235 and Thr274 regulated its subcellular distribution and function. VASP derivatives that lack the Ena/VASP homology 1 (EVH1) domain or contain a phosphoablative mutation of Ser153 were defective in restricting S. flexneri spread, indicating that the EVH1 domain and phosphorylation on Ser153 are required for this process. The EVH1 domain and Ser153 of VASP were required for VASP localization to focal adhesions, and localization of VASP to focal adhesions and/or the leading edge was required for restriction of spread. The contribution of the EVH1 domain was from both the donor and the recipient cell, whereas the contribution of Ser153 phosphorylation was only from the donor cell. Thus, unlike host proteins characterized in Shigella pathogenesis that promote bacterial spread, VASP and EVL function to limit it. The ability of VASP and EVL to limit spread highlights the critical role of focal adhesion complexes and/or the leading edge in bacterial passage between cells.

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Ena/VASP Proteins: Regulators of the Actin Cytoskeleton and Cell Migration

Cited by 604 publications

References 106 publications

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Involvement of vasodilator-stimulated phosphoprotein in UDP-induced microglial actin aggregation via PKC- and Rho-dependent pathways

Epigenetic silencing of the intronic microRNA hsa-miR-342 and its host gene EVL in colorectal cancer

Vasodilator-stimulated phosphoprotein restricts cell-to-cell spread of Shigella flexneri at the cell periphery

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