Rab38 regulates lamellar body size and number in lung alveolar type II cells

Abstract

The lung‐restricted small GTPase Rab38 has recently been shown to play key roles in surfactant trafficking and homeostasis in alveolar type II (ATII) cells. In this study, we found significantly enlarged but reduced number of lamellar bodies (LBs) in ATII cells isolated from Fawn‐hooded hypertension (FHH) rats containing a Rab38‐null mutation. This is accompanied by simplification of alveolar structures and thickening of lung small artery walls even in 10‐week‐old FHH rats. Interestingly, Rab38 expression is restricted to epithelium but not endothelium cells, and declines rapidly upon ATII cell culture. Transiently expressed EGFP‐Rab38, even at minimum expression level indicated by EGFP fluorescence close to background signals, consistently labels the limiting membranes of ~30% LBs in ATII cells isolated from WT and FHH rats. Such localization is abolished by point mutations (G19V & T23N) to the GTPase, suggesting the importance of an intact prenylation mechanism and GTPase activity. Consistently, we found endogenous Rab38 in the LB fraction isolated from the WT but not FHH rats. Importantly, reintroducing EGFP‐Rab38 back to the FHH ATII cells rescues the enlarged LB phenotype. Supported by NIH 5T32HL007748 and P01HL19737.