Defective CSF2RA causes SMDP4

Stable Identifier
Homo sapiens
Defective CSF2RA causes pulmonary surfactant metabolism dysfunction 4 (SMDP4)
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Surfactant catabolism by alveolar macrophages plays a small but critical part in surfactant recycling and metabolism. Upon ligand binding, granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR), a heterodimer of alpha (CSF2RA) and beta (CSF2RB) subunits, initiates a signalling process that not only induces proliferation, differentiation and functional activation of hematopoietic cells but can also determine surfactant uptake into alveolar macrophages and its degradation via clathrin-coated vesicles. Defects in human CSF2RA can cause pulmonary surfactant metabolism dysfunction 4 (SMDP4; MIM:300770, aka congenital pulmonary alveolar proteinosis, (PAP)), a rare lung disorder due to impaired surfactant homeostasis characterised by alveoli filling with floccular material. Cellular responses to the misfolded pro-SFTPC products include ER stress, the activation of reactive oxygen species and autophagy. Excessive lipoprotein accumulation in the alveoli results in a form of respiratory distress syndrome in premature infants (RDS; MIM:267450) (Whitsett et al. 2015).

Literature References
PubMed ID Title Journal Year
25621661 Diseases of pulmonary surfactant homeostasis

Whitsett, JA, Weaver, TE, Wert, SE

Annu Rev Pathol 2015
Name Identifier Synonyms
newborn respiratory distress syndrome DOID:12716 Neonatal respiratory Distress syndrome, hyaline membrane disease, HMD - Hyaline membrane disease, pulmonary hypoperfusion syndrome of newborn, respiratory distress syndrome of newborn, pulmonary hyaline membrane disease
pulmonary alveolar proteinosis DOID:12120
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