Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells

Vargas, Pablo Agustín; Maiuri, Paolo; Bretou, Marine; Saéz, Pablo; Pierobon, Paolo; Maurin, Mathieu; Chabaud, Mélanie; Lankar, Danielle; Obino, Dorian; Terriac, Emmanuel; Raab, Matthew; Thiam, Hawa Racine; Brocker, Thomas; Kitchen-Goosen, Susan M.; Alberts, Arthur S.; Sunareni, Praveen; Sheng, Xia; Li, Rong; Voituriez, Raphaël; Piel, Matthieu; Lennon-Duménil, Ana María

doi:10.1038/ncb3284

Cited by 181 publications

(283 citation statements)

References 49 publications

(70 reference statements)

Supporting

Mentioning

256

Contrasting

Order By: Relevance

“…In our hands, UO126 neither inhibited nor enhanced chemotaxis induced by either CCL19 or CCL21 (data not shown). A role for the Rho pathway in stimulation of murine DC chemotaxis in vitro and in vivo is supported by several studies (55, 56), and thus numerous pathways may be involved in controlling DC chemotaxis, and they may not be the same in 2D and 3D settings.…”

Section: Discussionmentioning

confidence: 94%

Differential CCR7 Targeting in Dendritic Cells by Three Naturally Occurring CC-Chemokines

et al. 2016

View full text Add to dashboard Cite

The CCR7 ligands CCL19 and CCL21 are increasingly recognized as functionally different (biased). Using mature human dendritic cells (DCs), we show that CCL19 is more potent than CCL21 in inducing 3D chemotaxis. Intriguingly, CCL21 induces prolonged and more efficient ERK1/2 activation compared with CCL19 and a C-terminal truncated (tailless) CCL21 in DCs. In contrast, tailless-CCL21 displays increased potency in DC chemotaxis compared with native CCL21. Using a CCL21-specific antibody, we show that CCL21, but not tailless-CCL21, accumulates at the cell surface. In addition, removal of sialic acid from the cell surface by neuraminidase treatment impairs ERK1/2 activation by CCL21, but not by CCL19 or tailless-CCL21. Using standard laboratory cell lines, we observe low potency of both CCL21 and tailless-CCL21 in G protein activation and β-arrestin recruitment compared with CCL19, indicating that the tail itself does not improve receptor interaction. Chemokines interact with their receptors in a stepwise manner with ultimate docking of their N-terminus into the main binding pocket. Employing site-directed mutagenesis we identify residues in this pocket of selective CCL21 importance. We also identify a molecular switch in the top of TM7 important for keeping CCR7 in an inactive conformation (Tyr312), as introduction of the chemokine receptor-conserved Glu (or Ala) induces high constitutive activity. Summarized, we show that the interaction of the tail of CCL21 with polysialic acid is needed for strong ERK signaling, whereas it impairs CCL21-mediated chemotaxis and has no impact on receptor docking consistent with the current model of chemokine:receptor interaction. This indicates that future selective pharmacological targeting of CCL19 versus CCL21 should focus on a differential targeting of the main receptor pocket, while selective targeting of tailless-CCL21 versus CCL21 and CCL19 requires targeting of the glycosaminoglycan (GAG) interaction.

show abstract

Section: Discussionmentioning

confidence: 94%

Differential CCR7 Targeting in Dendritic Cells by Three Naturally Occurring CC-Chemokines

et al. 2016

View full text Add to dashboard Cite

show abstract

“…This contrasts with the 'classic' gliding migration of fibroblasts or keratinocytes on 2D surfaces, which results from the dynamic protrusion of a lamellipodium at the front of the polarized cell and a contractile actomyosin network at its rear (Verkhovsky et al, 1999). Formins play a crucial role in generating and organizing the long actin cables that are necessary to support the elongated shape of the cells during 1D migration (Monzo et al, 2016;Vargas et al, 2016;Wilson et al, 2013), whereas Arp2/3 is more crucial for migration in 2D. Furthermore, if cell migration takes place on suspended electrospun nanofibers coated with ECM (Johnson et al, 2009), free actin waves propagate from the cell body to the tip of the cellular protrusion.…”

Section: Cell Migrationmentioning

confidence: 80%

How cells respond to environmental cues – insights from bio-functionalized substrates

Ruprecht

Monzo

Ravasio

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

Biomimetic materials have long been the (he)art of bioengineering. They usually aim at mimicking in vivo conditions to allow in vitro culture, differentiation and expansion of cells. The past decade has witnessed a considerable amount of progress in soft lithography, bioinspired micro-fabrication and biochemistry, allowing the design of sophisticated and physiologically relevant micro-and nanoenvironments. These systems now provide an exquisite toolbox with which we can control a large set of physicochemical environmental parameters that determine cell behavior. Biofunctionalized surfaces have evolved from simple protein-coated solid surfaces or cellular extracts into nano-textured 3D surfaces with controlled rheological and topographical properties. The mechanobiological molecular processes by which cells interact and sense their environment can now be unambiguously understood down to the single-molecule level. This Commentary highlights recent successful examples where bio-functionalized substrates have contributed in raising and answering new questions in the area of extracellular matrix sensing by cells, cell-cell adhesion and cell migration. The use, the availability, the impact and the challenges of such approaches in the field of biology are discussed.

show abstract

“…As opposed to fibroblasts and neural progenitor cells, evidence shows that Arp2/3-mediated actin polymerization inhibits the migration of both dendritic and T cells, which will be discussed below [50,51]. However, a recent study of dendritic cells suggests that successful passage through narrow pores, which is determined by the physical constraints of the nucleus, is associated with an increase in actin polymerization around the nucleus as it reaches the point of constriction [52].…”

Section: Introductionmentioning

confidence: 99%

“…A specific example of how the utilization of multiple nucleators contributes to cellular function comes from studies of dendritic cells (DCs) in confining microchannels. DCs have two competing pools of actin: a Cdc42- and Arp2/3-mediated accumulation of F-actin at the cell front that slows motility but is required for micropinocytosis and antigen uptake in immature DCs, and a RhoA- and mDia-mediated F-actin enrichment at the cell rear that is necessary for the fast migration and chemotaxis used by mature DCs to travel to the lymph nodes [51]. Stimulation with LPS, which triggers DC maturation, induces a switch from Arp2/3- to formin-derived actin networks with corresponding changes in migratory behavior [51].…”

Section: Introductionmentioning

confidence: 99%

“…DCs have two competing pools of actin: a Cdc42- and Arp2/3-mediated accumulation of F-actin at the cell front that slows motility but is required for micropinocytosis and antigen uptake in immature DCs, and a RhoA- and mDia-mediated F-actin enrichment at the cell rear that is necessary for the fast migration and chemotaxis used by mature DCs to travel to the lymph nodes [51]. Stimulation with LPS, which triggers DC maturation, induces a switch from Arp2/3- to formin-derived actin networks with corresponding changes in migratory behavior [51]. However, previous studies reported that depletion of Arp2/3 activators, including Cdc42 and WASP, impairs migration of DCs to the lymph nodes [93–95].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Function and regulation of the Arp2/3 complex during cell migration in diverse environments

Swaney

2016

Current Opinion in Cell Biology

Self Cite

View full text Add to dashboard Cite

As the first de novo actin nucleator discovered, the Arp2/3 complex has been a central player in models of protrusive force production via the dynamic actin network. Here, we review recent studies on the functional role of the Arp2/3 complex in the migration of diverse cell types in different migratory environments. These findings have revealed an unexpected level of plasticity, both in how cells rely on the Arp2/3 complex for migration and other physiological functions and in the intricate modulation of the Arp2/3 complex by other actin regulators and upstream signaling cascades.

show abstract

Innate control of actin nucleation determines two distinct migration behaviours in dendritic cells

Cited by 181 publications

References 49 publications

Differential CCR7 Targeting in Dendritic Cells by Three Naturally Occurring CC-Chemokines

Differential CCR7 Targeting in Dendritic Cells by Three Naturally Occurring CC-Chemokines

How cells respond to environmental cues – insights from bio-functionalized substrates

Function and regulation of the Arp2/3 complex during cell migration in diverse environments

Contact Info

Product

Resources

About