Morphological changes during dendritic cell maturation correlate with cofilin activation and translocation to the cell membrane

Abstract

Upon activation, tissue residing immature dendritic cells (DC) start to migrate towards the draining lymph node and mature into efficient antigen-presenting cells. During maturation DC loose their capacity to endocytose antigens, change their surface expression of adhesion molecules, chemokine receptors, and costimulatory molecules, and change morphology. We employed 2D-PAGE and mass spectrometry to identify additional differentially expressed proteins in immature and mature DC. Human monocyte-derived DC were matured with LPS and protein expression profiles were compared before and after maturation. One of the proteins differentially expressed between immature and mature DC was identified as the actin-binding protein cofilin. We show here that cofilin is dephosphorylated in response to several maturation stimuli (i.e. CD40 ligand, LPS or a combination of TNF- § and prostaglandin E 2 ). Moreover, dephosphorylated cofilin translocated towards the plasma membrane during maturation. Importantly, this correlated with an increase in filamentous actin and the appearance of veils, suggesting a role for cofilin in cytoskeletal rearrangements during maturation.

Dendritic Cell Motility and T Cell Activation Requires Regulation of Rho-Cofilin Signaling by the Rho-GTPase Activating Protein Myosin IXb

“…Interestingly, in the same study, cofilin was not enriched within the immunological synapse in B cells. However, Verdijk et al (42) reported translocation of cofilin toward submembranous regions in DCs in a stimulation-dependent manner, whereas we have observed an even distribution of cofilin within the cytosol of stimulated BMDCs (data not shown). Together, these findings suggest that cofilin may contribute to different degrees to immunological synapse formation in distinct APC populations.…”

Ultrastructural basis of enhanced antitumor cytotoxicity of cord blood-derived CTLs: A comparative analysis with peripheral blood and bone marrow

“…We plan to determine the significance of these cells using more advanced biochemical and immunological methods. Other than this anomaly, DCs from each source followed the expected progression of phenotype, supported by others (41). Immature DCs displayed long, thin dendritic processes, day 3 cells were a combination of veils and processes, mature DC displayed dense cytoplasmic veils on the cell surface, and day 10 cells were sparsely covered in veils.…”

“…We also noted a difference in nuclear size from day 0 to day 7 DCs, with the average nuclear size increasing as the DCs matured. This has been seen by others (39,41), and is due to an increase in cell size as a whole.…”

Tetraspanin KAI1/CD82 inhibits cell migration-related cellular events via reorganizing actin network

“…Scale bar, 20 µm. al., 1999;Nagata-Ohashi et al, 2004;Verdijk et al, 2004) Although cofilin still actively participated in membrane protrusion in both Du145-Mock and Du145-CD82 cells, Icouldn't determine whether cofilin is the primary driven force for membrane protrusion formation or not in this spectacular experiment. This is not a surprise to us as overexpression of cofilin may impair the actin cytoskeleton rearrangement and cell migration (Lee et al, 2005) or enhance the same process (Dang et al, 2006).…”

“…The two models are In addition to all these functions described above, the cofilin pathway contributes to morphogenesis, such as cell polarity in Drosophila (Blair et al, 2006), and blastocyst positioning and body wall formation . Driven by variety of stimuli, cofilin becomes dephosphorylated or activated, then translocated to the plasma membrane (Suzuki et al, 1995;Nagaishi et al, 1999;Nagata-Ohashi et al, 2004;Verdijk et al, 2004) where it interacts with the actin cytoskeleton and promotes actin cortical meshwork formation, actin recycling, and consequently lamellipodia formation (Raftopoulou and Hall, 2004).…”