Regulation of Directional Cell Motility in Alveolar Macrophages by a Formin Family Protein Fhod1

The actin cytoskeleton functions in various cellular events, including cell motility, morphogenesis, cytokinesis, and establishment and maintenance of cell polarity. Formin family proteins are structurally characterized by the presence of the formin homology domains (FH) 1 and 2, and play pivotal roles in actin filament assembly in a variety of cellular processes. Fhod3, a cardiac member of the family, is expressed abundantly in the heart and neurons, while Fhod1 is ubiquitously expressed. Fhod3 plays an essential role in cardiogenesis and neurogenesis. Fhod1 is known to contribute to the assembly of stress fibers, contractile actin structures found in cultured non-muscle cells. However, the in vivorole of Fhod1 remains poorly understood. Here we show that Fhod1 is abundantly expressed in the lung. Especially, alveolar macrophages isolated from bronchoalveolar lavage fluids were strongly stained with anti-Fhod1 antibodies. In Fhod1 KO mice, directional cell motility of alveolar macrophages was selectively impaired, suggesting the possibility that Fhod1-mediated actin assembly seems to promote cell polarization during cell migration. We will discuss roles of Fhod1 in the regulation of directed cell migration in alveolar macrophages.