mDia1 and WAVE2 Proteins Interact Directly with IRSp53 in Filopodia and Are Involved in Filopodium Formation

Goh, Wah Ing; Lim, Kim Buay; Sudhaharan, Thankiah; Sem, Kai Ping; Bu, Wenyu; Chou, Amy; Ahmed, Sohail

doi:10.1074/jbc.m111.305102

Cited by 88 publications

(101 citation statements)

References 58 publications

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“…Neuroblastoma Cells-In our previous work on filopodial formation and neuronal morphology, we detailed the lengths and lifetimes of filopodia in N1E-115 neuroblastoma cells as a model neuronal cell (11,15,25). We took a similar approach using N1E-115 neuroblastoma cells in this study to investigate the role of Dyn in filopodial formation.…”

Section: Dyn1-3 Localized To Lamellipodia and Filopodia In N1e-115mentioning

confidence: 99%

“…SH3 domains are protein-protein interaction sites that bind polyprolines. To date, the IRSp53 SH3 domain shows specificity for Wasp family verproline homologue (Wave) 1 and 2 (10), mammalian enabled (Mena) (9), neuronal Wiskott-Aldrich syndrome protein (N-WASP) (11), epidermal growth factor receptor pathway substrate 8 (Eps8) (12,13), and mDia1 and mDia2 (14,15). All of these IRSp53 SH3 domain partners have known roles in regulating actin dynamics.…”

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confidence: 99%

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Dynamin1 Is a Novel Target for IRSp53 Protein and Works with Mammalian Enabled (Mena) Protein and Eps8 to Regulate Filopodial Dynamics

Chou

Sem

Wright

et al. 2014

Journal of Biological Chemistry

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Background: IRSp53 generates filopodia by coupling membrane protrusion with actin dynamics through SH3 domain binding partners. Results: Dynamin1 interacts with IRSp53, and its GTPase and actin binding domains are required for filopodial formation. Conclusion: Dynamin1 plays a role in filopodial initiation and assembly. Significance: A novel role for dynamin1 in filopodial dynamics has implications for cell migration and wound healing.

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Section: Dyn1-3 Localized To Lamellipodia and Filopodia In N1e-115mentioning

confidence: 99%

mentioning

confidence: 99%

Dynamin1 Is a Novel Target for IRSp53 Protein and Works with Mammalian Enabled (Mena) Protein and Eps8 to Regulate Filopodial Dynamics

Chou

Sem

Wright

et al. 2014

Journal of Biological Chemistry

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“…IRSp53 has a Cdc42-binding site and an SH3 domain, both of which are crucial for filopodia formation (Krugmann et al, 2001;Govind et al, 2001). The IRSp53 SH3 domain interacts with Mena (also known as ENAH) (Krugmann et al, 2001), Eps8 (Disanza et al, 2006), WAVE2 (also known as WASF2) (Suetsugu et al, 2006;Goh et al, 2012), mDia1 (Goh et al, 2011) and dynamin 1 (Chou et al, 2014) to induce filopodia. These data led to a model for filopodia formation mediated by IRSp53 where membrane protrusion modulated by its I-BAR domain is coupled to actin polymerization modulated by its SH3-domain-binding partners .…”

Section: Introductionmentioning

confidence: 99%

The Rho GTPase Rif signals through IRTKS, Eps8 and WAVE2 to generate dorsal membrane ruffles and filopodia

Sudhaharan

Sem

Liew

et al. 2016

Journal of Cell Science

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Rif induces dorsal filopodia but the signaling pathway responsible for this has not been identified. We show here that Rif interacts with the I-BAR family protein IRTKS (also known as BAIAP2L1) through its I-BAR domain. Rif also interacts with Pinkbar (also known as BAIAP2L2) in N1E-115 mouse neuroblastoma cells. IRTKS and Rif induce dorsal membrane ruffles and filopodia. Dominant-negative Rif inhibits the formation of IRTKS-induced morphological structures, and Rif activity is blocked in IRTKS-knockout (KO) cells. To further define the Rif-IRTKS signaling pathway, we identify Eps8 and WAVE2 (also known as WASF2) as IRTKS interactors. We find that Eps8 regulates the size and number of dorsal filopodia and membrane ruffles downstream of Rif-IRTKS signaling, whereas WAVE2 modulates dorsal membrane ruffling. Furthermore, our data suggests that Tir, a protein essential for enterohemorrhagic Escherichia coli infection, might compete for Rif for interaction with the I-BAR domain of IRTKS. Based on this evidence, we propose a model in which Rho family GTPases use the I-BAR proteins, IRSp53 (also known as BAIAP2), IRTKS and Pinkbar, as a central mechanism to modulate cell morphology.

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“…Recently, mDia1, but not mDia2, was shown to be an important SH3 domain partner of IRSp53 in forming filopodia (Goh et al, 2012). In line with the emerging notion that there are multiple mechanisms regulating the formation of these structures, it is therefore possible that IRSp53 may participate in filopodia formation either through LIN7 or through mDia1, depending on cell context and different stimuli.…”

Section: Discussionmentioning

confidence: 64%

LIN7 regulates the filopodia and neurite promoting activity of IRSp53

Crespi¹,

Ferrari²,

Lonati³

et al. 2012

Journal of Cell Science

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SummaryThe insulin receptor substrate protein of 53 kDa (IRSp53) is crucially involved in the formation of filopodia and neurites through mechanisms that have only partially been clarified. We have investigated the role of the small scaffold protein LIN7, which interacts with IRSp53. We found that formation of actin-filled protrusions in neuronal NSC34 cells and neurites in neuroblastoma N2A cells depends on motifs mediating the LIN7:IRSp53 association, as both the coexpression of LIN7 with IRSp53 or the expression of the L27-IRSp53 chimera (a fusion protein between IRSp53 and the LIN7L27 domain for plasma membrane protein complexes association) prevented actin-deficient protrusions induced by overexpressed IRSp53, and enhanced the formation of actin-filled protrusions. The regulatory role of LIN7 in IRSp53-mediated extension of filopodia in neuronal N2A cells was demonstrated by live-cell imaging experiments. Moreover, LIN7 silencing prevented the extension of filopodia and neurites, induced by ectopic expression of IRSp53 or serum starvation, respectively, in undifferentiated and differentiated N2A cells. The expression of full-length IRSp53 or the LIN7DPDZ mutant lacking the domain for association with IRSp53 was unable to restore neuritogenesis in LIN7-silenced cells. Conversely, defective neuritogenesis could be rescued by the expression of RNAi-resistant full-length LIN7 or chimeric L27-IRSp53. Finally, LIN7 silencing prevented the recruitment of IRSp53 in Triton X-100-insoluble complexes, otherwise occurring in differentiated cells. Collectively these data indicate that LIN7 is a novel regulator of IRSp53, and that the association of these proteins is required to promote the formation of actin-dependent filopodia and neurites.

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mDia1 and WAVE2 Proteins Interact Directly with IRSp53 in Filopodia and Are Involved in Filopodium Formation

Cited by 88 publications

References 58 publications

Dynamin1 Is a Novel Target for IRSp53 Protein and Works with Mammalian Enabled (Mena) Protein and Eps8 to Regulate Filopodial Dynamics

Dynamin1 Is a Novel Target for IRSp53 Protein and Works with Mammalian Enabled (Mena) Protein and Eps8 to Regulate Filopodial Dynamics

The Rho GTPase Rif signals through IRTKS, Eps8 and WAVE2 to generate dorsal membrane ruffles and filopodia

LIN7 regulates the filopodia and neurite promoting activity of IRSp53

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