Cell and Tissue Research

, Volume 367, Issue 3, pp 481–493 | Cite as

The biology of the ABCA3 lipid transporter in lung health and disease

Review

Abstract

The lipid transporter, ATP-binding cassette class A3 (ABCA3), is a highly conserved multi-membrane-spanning protein that plays a critical role in the regulation of pulmonary surfactant homeostasis. Mutations in ABCA3 have been increasingly recognized as one of the causes of inherited pulmonary diseases. These monogenic disorders produce familial lung abnormalities with pathological presentations ranging from neonatal surfactant-deficiency-induced respiratory failure to childhood or adult diffuse parenchymal lung diseases for which specific treatment modalities remain limited. More than 200 ABCA3 mutations have been reported to date with approximately three quarters of patients presenting as compound heterozygotes. Recent advances in our understanding of the molecular basis underlying normal ABCA3 biosynthesis and processing and of the mechanisms of alveolar epithelial cell dysregulation caused by the expression of its mutant forms are beginning to emerge. These insights and the role of environmental factors and modifier genes are discussed in the context of the considerable variability in disease presentation observed in patients with identical ABCA3 gene mutations. Moreover, the opportunities afforded by an enhanced understanding of ABCA3 biology for targeted therapeutic strategies are addressed.

Keywords

ABCA3 Pulmonary surfactant Compound heterozygous mutations Surfactant deficiency Inhertited pulmonary disease 

Abbreviations

AT2

Alveolar type 2

LB

Lamellar body

ABCA3

ATP-binding cassette class A3

SP-C

Surfactant Protein C

SFTP(A, B, C, or D)

Gene encoding surfactant protein A, B, C, or D

DPLD

Diffuse parenchymal lung disease

IPF

Idiopathic pulmonary fibrosis

NBD

Nucleotide-binding domain

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© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Pulmonary, Allergy, and Critical Care Division, Department of Medicine, Surfactant Biology LaboratoriesUniversity of Pennsylvania Perelman School of MedicinePhiladelphiaUSA

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