FCHSD2 cooperates with CDC42 and N-WASP to regulate cell protrusion formation

Zhai, Xiaoyan; Shen, Yuxin; Zhang, Xiujuan; Li, Tianhao; Lü, Qing; Xu, Zhigang

doi:10.1016/j.bbamcr.2021.119134

Cited by 8 publications

(6 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The localization of FCHSD2 in mammalian cells has been studied primarily using exogenous protein, with reports indicating subcellular localization underneath the plasma membrane (Almeida-Souza et al ., 2018) and at actin protrusions (Zhai et al , 2022b). Given the role of MICAL-L1 in scaffolding endosome fission machinery, we hypothesized that some FCHSD2 might be transiently localized to endosomes.…”

Section: Resultsmentioning

confidence: 99%

“…We next addressed the potential mechanism by which FCHSD2 regulates endosome fission. Given the role of FCHSD2 in actin regulation and control of WASP (Almeida-Souza et al ., 2018; Becalska et al ., 2013; Rodal et al ., 2008; Stanishneva-Konovalova et al ., 2016; Zhai et al ., 2022b), we hypothesized that FCHSD2 may regulate fission by activation of ARP2/3 leading to actin polymerization and branching at the endosomal membrane, thus facilitating membrane budding. Indeed, treatment of cells with the ARP2/3 inhibitor, CK-666 (Nolen et al , 2009), led to impaired actin filament generation at RAB5 Q79L enlarged endosomes, whereas the CK-689 control had no effect on endosomal actin (EV4), highlighting the role of ARP2/3 in generating branched actin at endosomes.…”

Section: Resultsmentioning

confidence: 99%

“…Moreover, Nwk activates WASP to promote ARP2/3-dependent actin filament assembly (Stanishneva-Konovalova et al ., 2016), and similarly FCHSD2 stimulates ARP2/3 on flat membranes (Almeida-Souza et al ., 2018). FCHSD2 and CDC42 can also simultaneously bind N-WASP, providing an additional layer of actin regulation (Rodal et al ., 2008; Zhai et al ., 2022b). Given that the WASH complex is the major activator of endosomal ARP2/3 actin nucleation and WASH function is required for fission and receptor recycling (Derivery et al , 2012; Derivery et al ., 2009), it is logical to speculate that FCHSD2 activates WASH at endosomes to promote ARP2/3-based actin nucleation.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Endosomal actin branching, fission and receptor recycling require FCHSD2 recruitment by MICAL-L1

Frisby,

Murakonda,

Ashraf

et al. 2024

Preprint

View full text Add to dashboard Cite

Endosome fission is required for the release of carrier vesicles and the recycling of receptors to the plasma membrane. Early events in endosome budding and fission rely on actin branching to constrict the endosomal membrane, ultimately leading to nucleotide hydrolysis and enzymatic fission. However, our current understanding of this process is limited, particularly regarding the coordination between the early and late steps of endosomal fission. Here we have identified a novel interaction between the endosomal scaffolding protein, MICAL-L1, and the human homolog of theDrosophilaNervous Wreck (Nwk) protein, FCH and double SH3 domains protein 2 (FCHSD2). We demonstrate that MICAL-L1 recruits FCHSD2 to the endosomal membrane, where it is required for ARP2/3-mediated generation of branched actin, endosome fission and receptor recycling to the plasma membrane. Since MICAL-L1 first recruits FCHSD2 to the endosomal membrane, and is subsequently responsible for recruitment of the ATPase and fission protein EHD1 to endosomes, our findings support a model in which MICAL-L1 orchestrates endosomal fission by connecting between the early actin-driven and subsequent nucleotide hydrolysis steps of the process.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Endosomal actin branching, fission and receptor recycling require FCHSD2 recruitment by MICAL-L1

Frisby,

Murakonda,

Ashraf

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…TOCA-1 and other F-BAR domain proteins have well-described roles in endocytosis and promotion of positively curved membrane structures such as cytoplasmic tubular networks ( Frost et al, 2008 ; Taylor et al, 2019 ; Ledoux et al, 2023 ), but there are precedents for these and related BAR domain proteins acting in negatively curved membrane structures ( Qualmann and Kelly, 2000 ; She et al, 2002 ; Chitu et al, 2005 ; Guerrier et al, 2009 ; Shimada et al, 2010 ; Becalska et al, 2013 ; Zhai et al, 2022 ). This suggests that any membrane curvature preference of F-BAR domain proteins does not limit them to certain cellular functions.…”

Section: Discussionmentioning

confidence: 99%

Filopodial protrusion driven by density-dependent Ena–TOCA-1 interactions

Blake,

Fox,

Urbančič

et al. 2024

Journal of Cell Science

View full text Add to dashboard Cite

Filopodia are narrow actin-rich protrusions with important roles in neuronal development where membrane-binding adaptor proteins have emerged as upstream regulators that link membrane interactions to actin regulators, for example I-BAR and F-BAR domain-containing proteins interacting with Ena/VASP and formins. To explore the significance of the F-BAR neuronal membrane adaptor TOCA-1 in filopodia we used quantitative analysis of TOCA-1 and filopodial dynamics in Xenopus retinal ganglion cells, where Ena/VASP proteins have a native role in filopodial extension. Both the adaptors and their binding partners are part of diverse and redundant protein networks that can functionally compensate for each other. Increasing density of TOCA-1 enhances Ena/VASP binding in vitro and an accumulation of TOCA-1, and its coincidence with Ena, correlates with filopodial protrusion in vivo. Two-colour single molecule localisation microscopy of TOCA-1 and Ena supports their nanoscale association. TOCA-1 clusters promote filopodial protrusion depending on a functional SH3 domain and activation of Cdc42, which we perturbed using small molecule inhibitor CASIN. We propose that TOCA-1 clusters act independently of membrane curvature to recruit and promote Ena activity for filopodial protrusion.

show abstract

“…TOCA-1 and other membrane adaptors in filopodia formation TOCA-1 and other F-BAR proteins have well-described roles in endocytosis and promotion of positively curved membrane structures such as cytoplasmic tubular networks (Frost et al, 2008;Taylor et al, 2019). While the inverse F-BAR proteins SRGAP1-3 bind to negatively curved membrane like I-BAR proteins (Guerrier et al, 2009), positively curved F-BAR proteins have also been shown to induce, or localise to, membrane structures with mostly negative curvature such as filopodia (including Gas7 (She et al, 2002), PACSIN-1/-2 (Qualmann and Kelly, 2000;Shimada et al, 2010), Nwk (Becalska et al, 2013;Zhai et al, 2022)), suggesting that any membrane curvature preference of F-BAR proteins does not limit them to certain cellular functions. This could be possible because of alternative binding modes that target flat membrane (Frost et al, 2008;McDonald et al, 2015), or the presence of complex membrane curvatures for example those observed by EM in dendritic filopodial precursors (Galic et al, 2014) and described theoretically (Mancinelli et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Filopodial protrusion driven by density-dependent Ena-TOCA-1 interactions

Blake

Fox

Urbančič

et al. 2023

Preprint

View full text Add to dashboard Cite

Filopodia are narrow actin-rich protrusions with important roles in neuronal development. The neuronally-enriched TOCA-1/CIP4 family of F-BAR and SH3 domain adaptor proteins have emerged as upstream regulators that link membrane interactions to actin binding proteins in lamellipodia and filopodia, including WAVE and N-WASP nucleation promoting factors and formins. Here, we demonstrate a direct interaction between TOCA-1 and Ena/VASP actin filament elongators that is mediated by clustered SH3 domain interactions. Using Xenopus retinal gangion cell axonal growth cones, where Ena/VASP proteins have a native role in filopodia extension, we show that TOCA-1 localises to filopodia and lamellipodia with a retrograde flow of puncta and correlates with filopodial protrusion. Two-colour single molecule localization microscopy of TOCA-1 and Ena supports their nanoscale association. TOCA-1 clusters coalesce at advancing lamellipodia and filopodia and operate synergistically with Ena to promote filopodial protrusion dependent on a functional SH3 domain. In analogous yet distinct ways to lamellipodin and IRSp53, we propose that transient TOCA-1 clusters recruit and promote Ena activity to orchestrate filopodial protrusion.

show abstract

FCHSD2 cooperates with CDC42 and N-WASP to regulate cell protrusion formation

Cited by 8 publications

References 63 publications

Endosomal actin branching, fission and receptor recycling require FCHSD2 recruitment by MICAL-L1

Endosomal actin branching, fission and receptor recycling require FCHSD2 recruitment by MICAL-L1

Filopodial protrusion driven by density-dependent Ena–TOCA-1 interactions

Filopodial protrusion driven by density-dependent Ena-TOCA-1 interactions

Contact Info

Product

Resources

About