Rapidly rendering cells phagocytic through a cell surface display technique and concurrent Rac activation

• Published in: Science signaling 2014-07, Vol.7 (334), p.rs4-rs4
• Main Authors: Onuma, Hiroki, Komatsu, Toru, Arita, Makoto, Hanaoka, Kenjiro, Ueno, Tasuku, Terai, Takuya, Nagano, Tetsuo, Inoue, Takanari
• Format: Article
• Language: English
• Subjects: Antigens, Surface - metabolism; Cell Surface Display Techniques - methods; Cell Transdifferentiation - physiology; Cell- and Tissue-Based Therapy - methods; Dimerization; DNA Primers - genetics; Fluorescence; HeLa Cells; Humans; Jurkat Cells; Milk Proteins - metabolism; Phagocytosis - physiology; Phalloidine; Phosphatidylserines - metabolism; Plasmids - genetics; Protein Structure, Tertiary - physiology; rac1 GTP-Binding Protein - metabolism
• ISSN: 1945-0877; 1937-9145
• DOI: 10.1126/scisignal.2005123

Cell surfaces represent a platform through which extracellular signals that determine diverse cellular processes, including migration, division, adhesion, and phagocytosis, are transduced. Techniques to rapidly reconfigure the surface properties of living cells should thus offer the ability to harness these cellular functions. Although the molecular mechanism of phagocytosis is well characterized, the minimal molecular players that are sufficient to activate this elaborate process remain elusive. We developed and implemented a technique to present a molecule of interest at the cell surface in an inducible manner on a time scale of minutes. We simultaneously induced the cell surface display of the C2 domain of milk fat globule epidermal growth factor factor 8 (MFG-E8) and activated the intracellular small guanosine triphosphatase Rac, which stimulates actin polymerization at the cell periphery. The C2 domain binds to phosphatidylserine, a lipid exposed on the surface of apoptotic cells. By integrating the stimulation of these two processes, we converted HeLa cells into a phagocytic cell line that bound to and engulfed apoptotic human Jurkat cells. Inducing either the cell surface display of the C2 domain or activating Rac alone was not sufficient to stimulate phagocytosis, which suggests that attachment to the target cell and actin reorganization together constitute the minimal molecular events that are needed to induce phagocytosis. This cell surface display technique might be useful as part of a targeted, cell-based therapy in which unwanted cells with characteristic surface molecules could be rapidly consumed by engineered cells.