New proteins responsible for the interaction between phagosomes and F-Actin and their role in macrophage function

• Applicant: Privatdozent Dr. Sergei A. Kuznetsov
• Subject Area: Cell Biology
• Term: from 2005 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 12775306

Phagosome interaction with the cytoskeleton plays a key role in phagosome maturation which leads to pathogen killing. We developed an in vitro binding assay to analyze how in model system latex bead loaded phagosomes bind to F-actin. Three cytoplasmic factors were found to be involved in the interactions between F-actin and phagosomes. One factor responsible for the ATP-dependent binding was identified as myosin Va. This myosin bound to phagosomes was shown to delay microtubule-dependent retrograde phagosome movement toward the cell center. The goal of this proposal is to identify the other two factors: a high molecular weight (> 600 kDa) actin-binding protein (HMWABP) responsible for the ATP-independent binding of LBPs to F-actin, and a small (s 15-25 kDa) cytosolic protein that inhibits association of both myosin Va and HMWABP with phagosomes. The role of myosin V and the newly identified factors in the regulation of phagosome interaction with F-actin and in phagosome biogenesis will then be analyzed in vivo.

• DFG Programme: Research Grants