GM130 regulates pulmonary surfactant protein secretion in alveolar type II cells

Abstract

Pulmonary surfactant is a lipid-protein complex secreted by alveolar type II epithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across the air-liquid barrier. The Golgi apparatus plays an important role in pulmonary surfactant modification and secretory trafficking. However, the physiological function of the Golgi apparatus in the transport of pulmonary surfactants is unclear. In the present study, deletion of GM130, which encodes for a matrix protein of the cis-Golgi cisternae, was shown to induce the disruption of the Golgi structure leading to impaired secretion of lung surfactant proteins and lipids. Specifically, the results of in vitro and in vivo analysis indicated that the loss of GM130 resulted in trapping of Sftpa in the endoplasmic reticulum, Sftpb and Sftpc accumulation in the Golgi apparatus, and an increase in the compensatory secretion of Sftpd. Moreover, global and epithelial-specific GM130 knockout in mice resulted in an enlargement of alveolar airspace and an increase in alveolar epithelial autophagy; however, surfactant repletion partially rescued the enlarged airspace defects in GM130-deficient mice. Therefore, our results demonstrate that GM130 and the mammalian Golgi apparatus play a critical role in the control of surfactant protein secretion in pulmonary epithelial cells.

Prmt5 promotes ciliated cell specification of airway epithelial progenitors via transcriptional inhibition of Tp63

“…Sectional AB-PAS and H&E staining were performed as described previously ( 51 ). Briefly, tracheas isolated from E18.5 control and Prmt5 fl/fl ;Shh Cre/+ mice were fixed in 4% paraformaldehyde (PFA, Sigma-Aldrich, P6148) overnight at 4 °C, then processed to paraffin (Thermo Fisher Scientific, 8330) embedding and sectioned at 5 μm thickness.…”

“…The ventral side of the tracheas was then analyzed without a conductive coating by using a Zeiss EVO 15 SEM (Carl Zeiss Microscopy GmbH). TEM assay was performed as previously reported ( 51 ). Briefly, isolated tracheas were fixed in 2.5% glutaraldehyde and then in 1% OsO4 on ice for 2 h, dehydrated in graded acetone solutions and embedded in EMbed 812 resin (Electron Microscopy Sciences, 13940).…”

Repetitive DNA Sequences in the Human Y Chromosome and Male Infertility

“…Reports have indicated that the gene is only transcribed in the testis and expresses a protein of 108 amino acids ( Skaletsky et al, 2003 ; Jangravi et al, 2013 ; Alechine and Corach, 2014 ), although the two copies may have different roles in spermatogenesis ( Noordam et al, 2011 ; Lu et al, 2014 ). GOLGA2 is a Golgi matrix protein that is essential for the processing and transport of specific proteins by the Golgi ( Liu C. et al, 2017 ; Pang et al, 2021b ). Moreover, the deletion of GOLGA2 can cause male sterility by regulating the function of the acrosome ( Han et al, 2017 ).…”

PRMT7 targets of Foxm1 controls alveolar myofibroblast proliferation and differentiation during alveologenesis

“…For rescue experiments, MYFs at 60-70% confluence were transfected with the pCMV-Tag2B-Foxm1 or empty vector using Lipofectamine TM 2000 (Invitrogen, 11668019) as described previously [50]. In brief, replace the growth medium before 1 h of the transfection, mixed the plasmids and transfection reagents at 1:3 ratios, and incubated for 20 min at room temperature before added to the cells.…”