LAMP3 deficiency affects surfactant homeostasis in mice.
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 r...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2021-06-01
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| Series: | PLoS Genetics |
| Online Access: | https://doi.org/10.1371/journal.pgen.1009619 |
| _version_ | 1818585623867424768 |
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| author | Lars P Lunding Daniel Krause Guido Stichtenoth Cordula Stamme Niklas Lauterbach Jan Hegermann Matthias Ochs Björn Schuster Radislav Sedlacek Paul Saftig Dominik Schwudke Michael Wegmann Markus Damme |
| author_facet | Lars P Lunding Daniel Krause Guido Stichtenoth Cordula Stamme Niklas Lauterbach Jan Hegermann Matthias Ochs Björn Schuster Radislav Sedlacek Paul Saftig Dominik Schwudke Michael Wegmann Markus Damme |
| author_sort | Lars P Lunding |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-16T08:40:01Z |
| format | Article |
| id | doaj.art-530766cbc3c546f5bac9311145dd3f03 |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-16T08:40:01Z |
| publishDate | 2021-06-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-530766cbc3c546f5bac9311145dd3f032022-12-21T22:37:42ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042021-06-01176e100961910.1371/journal.pgen.1009619LAMP3 deficiency affects surfactant homeostasis in mice.Lars P LundingDaniel KrauseGuido StichtenothCordula StammeNiklas LauterbachJan HegermannMatthias OchsBjörn SchusterRadislav SedlacekPaul SaftigDominik SchwudkeMichael WegmannMarkus DammeLysosome-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.https://doi.org/10.1371/journal.pgen.1009619 |
| spellingShingle | Lars P Lunding Daniel Krause Guido Stichtenoth Cordula Stamme Niklas Lauterbach Jan Hegermann Matthias Ochs Björn Schuster Radislav Sedlacek Paul Saftig Dominik Schwudke Michael Wegmann Markus Damme LAMP3 deficiency affects surfactant homeostasis in mice. PLoS Genetics |
| title | LAMP3 deficiency affects surfactant homeostasis in mice. |
| title_full | LAMP3 deficiency affects surfactant homeostasis in mice. |
| title_fullStr | LAMP3 deficiency affects surfactant homeostasis in mice. |
| title_full_unstemmed | LAMP3 deficiency affects surfactant homeostasis in mice. |
| title_short | LAMP3 deficiency affects surfactant homeostasis in mice. |
| title_sort | lamp3 deficiency affects surfactant homeostasis in mice |
| url | https://doi.org/10.1371/journal.pgen.1009619 |
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