Arp2/3 complex activity in filopodia of spreading cells

Johnston, Simon A.; Bramble, Jonathan P.; Yeung, Chun L.; Mendes, Paula M.; Machesky, Laura M.

doi:10.1186/1471-2121-9-65

Cited by 57 publications

(42 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These structures are also decorated with Arp2/3 complexes and cortactin in the absence of any evident F-actin branching ( Fig. 3D and E), a Rac1-dependent feature previously described by others in filopodia (27). In vivo staining of cells with Clostridium botulinum toxin B revealed that the majority of lipid rafts cosegregate with these Rac1/F-actin-rich structures present in knockdown cells (Fig.…”

Section: Coro1-deficient Cells Show Abnormal Shapes and Contractilesupporting

confidence: 73%

Coronin1 Proteins Dictate Rac1 Intracellular Dynamics and Cytoskeletal Output

Ojeda

Castro-Castro

Bustelo

2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

Rac1 regulates lamellipodium formation, myosin II-dependent contractility, and focal adhesions during cell migration. While the spatiotemporal assembly of those processes is well characterized, the signaling mechanisms involved remain obscure. We report here that the cytoskeleton-related Coronin1A and -1B proteins control a myosin II inactivation-dependent step that dictates the intracellular dynamics and cytoskeletal output of active Rac1. This step is signaling-branch specific, since it affects the functional competence of active Rac1 only when forming complexes with downstream ArhGEF7 and Pak proteins in actomyosin-rich structures. The pathway is used by default unless Rac1 is actively rerouted away from the structures by upstream activators and signals from other Rho GTPases. These results indicate that Coronin1 proteins are at the center of a regulatory hub that coordinates Rac1 activation, effector exchange, and the F-actin organization state during cell signaling. Targeting this route could be useful to hamper migration of cancer cells harboring oncogenic RAC1 mutations.

show abstract

Section: Coro1-deficient Cells Show Abnormal Shapes and Contractilesupporting

confidence: 73%

Coronin1 Proteins Dictate Rac1 Intracellular Dynamics and Cytoskeletal Output

Ojeda

Castro-Castro

Bustelo

2014

Molecular and Cellular Biology

View full text Add to dashboard Cite

show abstract

“…Thus, in cultured Drosophila cells, RNAi-mediated depletion of SCAR, the only member of the WAVE subfamily of Arp2/3 complex activators, strongly inhibited both lamellipodia and filopodia. 57 Inhibition of filopodia was also observed after expression of dominant negative Rac1 in cultured fibroblasts, 58 and in developing Drosophila…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 98%

Filopodia initiation

Yang¹,

Svitkina

2011

Cell Adhesion & Migration

170

View full text Add to dashboard Cite

“…This model appears to be in line with earlier observations of (i) the requirement of actin polymerization for the formation of filopodia (62,81,84), which is driven at least by mDia1 and mDia2 formins in a variety of cell types (85)(86)(87)(88), (ii) the detection of specific accumulations of formins at filopodial tips by fluorescence microscopy (39,85,86,88,89), (iii) the proposed repetitive nucleation of actin polymerization at the filopodium tip (60,62,80,84), which is followed by rearrangement/bundling of filaments within the extending filopodial shaft (90), (iv) the localization of Arp2/3 complex-containing dots along filopodia in mouse embryonic fibroblasts (91), and (v) the coexistence of Arp2/3-generated branched networks and longitudinal actin filaments in cell protrusions, as demonstrated by ultrastructural analysis of invadopodia of human metastatic cancer cells (92).…”

Section: Discussionmentioning

confidence: 99%

The Formins FMNL1 and mDia1 Regulate Coiling Phagocytosis of Borrelia burgdorferi by Primary Human Macrophages

et al. 2013

View full text Add to dashboard Cite

Spirochetes of the Borrelia burgdorferi sensu lato complex are the causative agent of Lyme borreliosis, a tick-borne infectious disease primarily affecting the skin, nervous system, and joints. During infection, macrophages and dendritic cells are the first immune cells to encounter invading borreliae. Phagocytosis and intracellular processing of Borrelia by these cells is thus decisive for the eventual outcome of infection. Phagocytic uptake of Borrelia by macrophages proceeds preferentially through coiling phagocytosis, which is characterized by actin-rich unilateral pseudopods that capture and enwrap spirochetes. Actin-dependent growth of these pseudopods necessitates de novo nucleation of actin filaments, which is regulated by actin-nucleating factors such as Arp2/3 complex. Here, we demonstrate that, in addition, also actin-regulatory proteins of the formin family are important for uptake of borreliae by primary human macrophages. Using immunofluorescence, live-cell imaging, and ratiometric analysis, we find specific enrichment of the formins FMNL1 and mDia1 at macrophage pseudopods that are in contact with borreliae. Consistently, small interfering RNA (siRNA)-mediated knockdown of FMNL1 or mDia1 leads to decreased formation of Borrelia-induced pseudopods and to decreased internalization of borreliae by macrophages. Our results suggest that macrophage coiling phagocytosis is a complex process involving several actin nucleation/regulatory factors. They also point specifically to the formins mDia1 and FMNL1 as novel regulators of spirochete uptake by human immune cells.

show abstract

Arp2/3 complex activity in filopodia of spreading cells

Cited by 57 publications

References 35 publications

Coronin1 Proteins Dictate Rac1 Intracellular Dynamics and Cytoskeletal Output

Coronin1 Proteins Dictate Rac1 Intracellular Dynamics and Cytoskeletal Output

Filopodia initiation

The Formins FMNL1 and mDia1 Regulate Coiling Phagocytosis of Borrelia burgdorferi by Primary Human Macrophages

Contact Info

Product

Resources

About