Phagocytosis depends on reorganization of cortical actin coordinated with the recruitment of intracellular compartments, which fuse with the plasma membrane, a process necessary to for actin dynamics and efficient particle internalization (Niedergang and Grinstein, 2018). We showed that mDia1, an actin nucleator of the formin family, is required downstream of the CR3 integrin receptors and highlighted an original dialogue between the microtubules and actin (Colucci-Guyon et al., 2005; Lewkowicz et al., 2008). We revealed recently that the negative Arp2/3 regulator Arpin is required for efficient phagosome formation (Jubrail et al., 2020).  We identified the B cell lymphoma/leukemia-10 (Bcl10) protein, as unexpectedly involved in actin dynamics by controlling trafficking and signaling during phagocytosis (Marion et al., 2012). We developed an original method based on evanescent wave microscopy to monitor the spatiotemporal location of molecular players in nascent phagosomes in three dimensions (Marie-Anais et al., 2016a), which allowed us to identify that dynamin2 is crucial to control phagosome formation and closure (Marie-Anais et al., 2016b; Mularski et al., 2021).

We now study in details early steps of phagocytic receptors clustering and force generation (Mularski and Niedergang, 2019), taking advantage of unique deformable lipid droplets, in collaboration with Jacques Fattaccioli (Laboratoire microfluidique Institut Pierre Gilles de Gennes – CNRS, ENS, Sorbonne Université) and Jean-Maurice MALLET (Laboratoire des Biomolécules, CNRS, ENS, Sorbonne Université) in the context of a CNRS 80 PRIME programme and ANR PhagoChemiForce. We also analyze the fate of ingested materials leading to their degradation.

References

  1. Niedergang, F., and Grinstein, S. (2018). How to build a phagosome: new concepts for an old process. Curr Opin Cell Biol 50, 57-63.
  2. Depierre, M., Jacquelin, L. and Niedergang, F. Phagocytosis in Encyclopedia of Cell Biology, in press.
  3. Colucci-Guyon, E., Niedergang, F., Wallar, B.J., Peng, J., Alberts, A.S., and Chavrier, P. (2005). A role for mammalian diaphanous-related formins in complement receptor (CR3)-mediated phagocytosis in macrophages. Curr Biol 15, 2007-2012.
  4. Lewkowicz, E., Herit, F., Le Clainche, C., Bourdoncle, P., Perez, F., and Niedergang, F. (2008). The microtubule-binding protein CLIP-170 coordinates mDia1 and actin reorganization during CR3-mediated phagocytosis. J Cell Biol 183, 1287-1298.
  5. Marion, S., Mazzolini, J., Herit, F., Bourdoncle, P., Kambou-Pene, N., Hailfinger, S., Sachse, M., Ruland, J., Benmerah, A., Echard, A., et al. (2012). The NF-kappaB Signaling Protein Bcl10 Regulates Actin Dynamics by Controlling AP1 and OCRL-Bearing Vesicles. Dev Cell 23, 954-967.
  6. Marie-Anais, F., Mazzolini, J., Bourdoncle, P., and Niedergang, F. (2016). "Phagosome Closure Assay" to Visualize Phagosome Formation in Three Dimensions Using Total Internal Reflection Fluorescent Microscopy (TIRFM). J Vis Exp.
  7. Marie-Anais, F., Mazzolini, J., Herit, F., and Niedergang, F. (2016). Dynamin-Actin Cross Talk Contributes to Phagosome Formation and Closure. Traffic 17, 487-499.
  8. Jubrail, J., Africano-Gomez, K., Herit, F., Mularski, A., Bourdoncle, P., Oberg, L., Israelsson, E., Burgel, P.R., Mayer, G., Cunoosamy, D.M., et al. (2020). Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus. EMBO Rep 21, e47963.
  9. Anna Mularski and Florence Niedergang (2020). Force Measurement of Living Professional Phagocytes of the Immune System. Australian Journal of Chemistry - https://doi.org/10.1071/CH19409