Drebrin Is Required for Myosin-facilitated Actin Cytoskeletal Remodeling During Pulmonary Alveolar Development

Am J Respir Cell Mol Biol. 2024 Jan 25. doi: 10.1165/rcmb.2023-0229OC. Online ahead of print.ABSTRACTAlveolar septation increases gas-exchange surface area and requires coordinated cytoskeletal rearrangement in lung fibroblasts (LF), to balance the demands of contraction and cell migration. We hypothesized that drebrin (DBN), a modulator of the actin cytoskeleton in neuronal dendrites, regulates the remodeling of the LF-cytoskeleton. Using mice bearing a transgelin-Cre (TGCre) targeted deletion of Dbn in pulmonary fibroblasts and pericytes, we examined alterations in alveolar septal outgrowth, LF spreading and migration, and actomyosin function. The alveolar surface area and number of alveoli were reduced whereas alveolar ducts were enlarged in mice bearing the dbn deletion (DBNΔ) compared to their littermates bearing only one dbn-Flox allele (control). Cultured DBNΔ LF were deficient in their responses to substrate rigidity and migrated more slowly. Drebrin was abundant in the actin cortex and lamella and the actin fiber orientation was less uniform in lamella of DBNΔ LF, which limited the development of traction forces and altered focal adhesion dynamics. Actin fiber orientation is regulated by contractile non-muscle myosin (NM2) motors which help arrange actin stress fibers (SF) into thick ventral actin SF. Using fluorescence anisotropy, we observed regional intracellular differences in myosin regulatory light chain phosphorylation in control LF that were altered by dbn...
Source: Am J Respir Cell Mol... - Category: Respiratory Medicine Authors: Source Type: research