LAMP3 deficiency affects surfactant homeostasis in mice

0544154 - ÚMG 2022 RIV US eng J - Journal Article
Lunding, L.P. - Krause, D. - Stichtenoth, G. - Stamme, C. - Lauterbach, N. - Hegermann, J. - Ochs, M. - Schuster, Bjorn - Sedláček, Radislav - Saftig, P. - Schwudke, D. - Wegmann, M. - Damme, M.
LAMP3 deficiency affects surfactant homeostasis in mice.
PLoS Genetics. Roč. 17, č. 6 (2021), č. článku e1009619. ISSN 1553-7404. E-ISSN 1553-7404
R&D Projects: GA MŠMT(CZ) LM2018126
Institutional support: RVO:68378050
Keywords : pulmonary surfactant * respiratory-failure * mass-spectrometry * membrane-proteins * marker * phosphatidylcholine * maturation * cloning
OECD category: Biochemistry and molecular biology
Impact factor: 6.020, year: 2021
Method of publishing: Open access
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009619

Lysosome-associated membrane glycoprotein 3 (LAMP3) is a type I transmembrane protein of the LAMP protein family with a cell-type-specific expression in alveolar type II cells in mice and hitherto unknown function. In type II pneumocytes, LAMP3 is localized in lamellar bodies, secretory organelles releasing pulmonary surfactant into the extracellular space to lower surface tension at the air/liquid interface. The physiological function of LAMP3, however, remains enigmatic. We generated Lamp3 knockout mice by CRISPR/Cas9. LAMP3 deficient mice are viable with an average life span and display regular lung function under basal conditions. The levels of a major hydrophobic protein component of pulmonary surfactant, SP-C, are strongly increased in the lung of Lamp3 knockout mice, and the lipid composition of the bronchoalveolar lavage shows mild but significant changes, resulting in alterations in surfactant functionality. In ovalbumin-induced experimental allergic asthma, the changes in lipid composition are aggravated, and LAMP3-deficient mice exert an increased airway resistance. Our data suggest a critical role of LAMP3 in the regulation of pulmonary surfactant homeostasis and normal lung function.
Permanent Link: http://hdl.handle.net/11104/0321194