The role of cytoskeletal proteins ADF/cofilin1 in microglia morphology and function
1 Neuroimmunology & Imaging Group, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
2 Axon Growth and Regeneration Group, German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany
3 Cellular Neuropathology and Cognition, IEECR, University clinics Bonn, Life & Brain Center, Germany
4 Institute for Genetics, University of Bonn, Germany
Microglia, the resident immune cells of the central nervous system, play a vital role in maintaining homeostatic balance and responding to disease. Additionally, they contribute to brain development, neuronal interactions, and higher brain functions. These highly motile cells continually survey the brain parenchyma using protrusions, yet the precise cellular mechanisms governing their dynamic shape changes are not fully understood. The cytoskeletal proteins actin depolymerizing factor and cofilin 1 (ADF/Cfl1) have established significance in neuronal development, function, and cell cycle control through their role in actin filaments reorganization. However, their specific role in microglia remains unexplored. We generated a mouse line with an inducible conditional Adf/Cfl1 knockout in microglia in the adult brain. Knockout of ADF/Cfl1 resulted in distinct changes in cellular morphology in vivo and ex vivo, as well as accumulation of filamentous actin. Additionally, in vivo imaging revealed reduced motility of microglia fine processes, as well as impaired migration towards a laser lesion in absence of ADF/Cfl1 in microglia. Knockout of ADF/Cfl1 also resulted in an immune response in the brain, with increased proliferation of microglia, upregulation of CD45 and MHC II, along with T cell recruitment. The findings from our study attribute a vital function of ADF/Cfl1 to the morphology and function of microglia, both in states of health and disease. Furthermore, our data indicates that the presence of ADF/Cfl1 is essential for maintaining the integrity of microglia, ensuring proper morphology and function in the brain.