Movement within and movement beyond: synaptotagmin-mediated vesicle fusion during chemotaxis

Abstract

Leukocyte chemotaxis plays an essential role in generating and delivering immune responses and is a critical component of inflammation. In order to identify novel genes and pathways important for regulating chemotaxis, we performed an RNAi-based screen and identified several genes involved with vesicle movement and fusion as mediators of chemotaxis. Our recently published data show that during chemotaxis vesicle trafficking proteins are required for lysosome fusion, uropod release and efficient directed cell migration.

Figure 1

Transwell chemotaxis of SupT1 cells infected with viruses containing shRNA targeting genes encoding the indicated members of the Rab family or EGFP as a control. The number of cells migrating to the lower chamber was determined using CyQUANT as previously described. Reductions in the chemokine dose response were significant using ANOVA (p < 0.01 for each of the knock-down cell lines).

Figure 2

Model of SYT7 activity in chemotaxis. Following the binding of a chemoattractant (eg. chemokine) to its G protein-coupled seven transmembrane spanning receptor, calcium is released. Binding of calcium to Syt7 on the lysosome surface induces Vamp7 on the lysosome surface to interact with Syn-4 and SNAP-23 at the cell membrane thereby facilitating the fusion of the lysosome with the cell membrane.