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The actin-nucleating protein Fhod1 in alveolar macrophages

The formin family proteins are a family of actin-nucleating protein conserved in eukaryotes from yeast to human. Among them, the formin homology domain-containing protein (Fhod) subfamily of formins emerged prior to the evolution of the metazoa and duplicated into Fhod1 and Fhod3 in vertebrates. Fhod3 plays an essential role in the assembly of actin into myofibrils in cardiomyocytes. Fhod1, on the other hand, contributes to the assembly of stress fibers, contractile actin structures found in cultured non-muscle cells. However, the in vivo role of Fhod1 remains poorly understood. To address this issue, we replaced the Fhod1 gene in mice with a lacZ reporter gene. Histological lacZ staining revealed strong expression of Fhod1 in the lung from embryonic day 12.5. Among the lung tissues, Fhod1 is expressed abundantly in alveolar macrophages. Alveolar macrophages isolated from bronchoalveolar lavage fluids of Fhod1 KO mice showed abnormal appearance and impaired cell motility. Thus, Fhod1 appears to be required for normal function of alveolar macrophages. We will discuss roles of Fhod1 in the regulation of actin dynamics in alveolar macrophages and the maintenance of normal lung function.