Source: International Congress 2014 – ILDs 3
Disease area: Interstitial lung diseases, Paediatric lung diseases

Abstract

Background and aim: ABCA3 is a surfactant lipid transporter in the limiting membrane of lamellar bodies in alveolar type II cells. Mutations in the ABCA3 gene cause respiratory distress syndrome in newborns and chronic interstitial lung disease in children and adults. ABCA3 belongs to the class of full ABC-transporters, which are supposed to be functional in their monomeric forms. Though other family members e.g. ABCA1 and ABCC7 have been shown to function as oligomers, the oligomerization state of ABCA3 remains to be elucidated.Methods: Oligomerization of ABCA3 was investigated in cell lysates and crude membrane preparations from transiently and stably transfected HEK293 cells using blue native PAGE (BN-PAGE), gel filtration and co-immunoprecipitation. Additionally, homooliomerization was examined in vivo in cells using bioluminescence resonance energy transfer (BRET).Results: Using BN-PAGE and gel filtration, methods that separate proteins in their native state according to their molecular size, we could show that non-denatured ABCA3 exists in different oligomeric forms, such as monomers, dimers, tetramers and even higher oligomers. Homooligomerization of ABCA3-wildtype was shown via co-immunoprecipitation of HA- and YFP-tagged ABCA3. Oligomerization could be verified in vivo by detecting positive interactions using BRET.Conclusion: Besides its monomeric state, ABCA3 was detected in additional oligomeric forms. We therefore suggest transporter oligomerization as a central mechanism for ABCA3 function. Insights into the fundamentals of the transport process will provide a better understanding of ABCA3-related diseases and enable the analysis of patient mutations and its interactions.

Rating:

Share or cite this content

Citations should be made in the following way:
S. Frixel, E. Kaltenborn, A. S. Lotz-Havla, S. W. Gersting, R. Zarbock, M. Griese (Munich, Germany). Homooligomerization of the ABC-transporter 3 and its functional significance. Eur Respir J 2014; 44: Suppl. 58, 790

Member's Comments

No comment yet.

Related content which might interest you: Outcome of acute drug-induced pneumonias in ICU Source: Annual Congress 2013 –Diffuse parenchymal lung disease II Year: 2013 Expression of water and ion channels proteins in acute respiratory distress syndrome from different etiologies Source: International Congress 2014 – Experimental models in acute lung injury Year: 2014 Dysfunction of oxidized pulmonary surfactant is cholesterol-dependent Source: Annual Congress 2013 –The multiple faces of stress in lung injury Year: 2013 Markers of poor outcome in patients with acute hypoxemic respiratory failure Source: International Congress 2014 – ICU outcomes, sepsis and infections Year: 2014 Essential oils reduced lung inflammation in a model of acute lung injury Source: International Congress 2014 – Experimental models in acute lung injury Year: 2014 Septic pulmonary embolisms as a cause of acute respiratory distress syndrome Source: International Congress 2016 – Pulmonary hypertension in lung disease Year: 2016 Assessing regional PEEP-related airway opening and dilatation in ARDS patients Source: International Congress 2015 – Acute critical care: mechanical ventilation: how to limit the damage Year: 2015 Radiologic features of lung involvement in young patients with viral pneumonia Source: International Congress 2016 – Mixed-up imaging of various chest diseases Year: 2016 Lung recruitment maneuver with and without nebulized albuterol for acute lung injury Source: International Congress 2014 – ARDS, skeletal muscles, physiology and weaning Year: 2014 Long-term effects of nebulized LPS in a mouse model of acute lung injury (ALI) Source: International Congress 2014 – ILDs 6 Year: 2014 Lung inflammation was attenuated by sakuranetin treatment in a model of acute lung injury Source: International Congress 2014 – Experimental models in acute lung injury Year: 2014 Methotrexate reduces acute lung injury in a murine model of sepsis Source: International Congress 2016 – Infections, sepsis, and pulmonary embolism Year: 2016 LATE-BREAKING ABSTRACT: Trasplantation of alveolar type II cells in experimental Acute Lung Injury Source: International Congress 2014 – Lung cell biology in injury and repair Year: 2014 Acute respiratory distress syndrome in patients admitted for community-acquired pneumonia Source: International Congress 2014 – ARDS, skeletal muscles, physiology and weaning Year: 2014 Effects of nebulized heparin in a rat-model of endotoxemia-induced lung injury Source: International Congress 2014 – Critical illness and therapeutic interventions Year: 2014 Clinical and microbiological characteristics and outcome of ARDS in India Source: International Congress 2016 – Dealing with the complexity of critically-ill patients Year: 2016 Morbi-mortality evaluation in prolonged prone positioning during severe ARDS Source: International Congress 2015 – Acute critical care: novelties in critical care Year: 2015 Obesity is associated with airspace lipid dysregulation Source: International Congress 2016 – Translational studies in lung disease Year: 2016 Lung protective ventilator settings for lung transplantation? The Harefield experience Source: Annual Congress 2013 –Clinical studies in lung transplantation Year: 2013 Amphetamine induced eosinophilic pneumonia: A case report Source: International Congress 2014 – ILDs 6 Year: 2014