title: The ABCC6 transporter: what lessons can be learnt from other ATP-binding cassette transporters?
abstract: ABC transporters represent a large family of ATP-driven transmembrane transporters involved in uni- or bidirectional transfer of a large variety of substrates. Divided in seven families, they represent 48 transporter proteins, several of which have been associated with human disease. Among the latter is ABCC6, a unidirectional exporter protein primarily expressed in liver and kidney. ABCC6 deficiency has been shown to cause the ectopic mineralization disorder pseudoxanthoma elasticum (PXE), characterized by calcification and fragmentation of elastic fibers, resulting in oculocutaneous and cardiovascular symptoms. Unique in the group of connective tissue disorders, the pathophysiological relation between the ABCC6 transporter and ectopic mineralization in PXE remains enigmatic, not in the least because of lack of knowledge on the substrate(s) of ABCC6 and its unusual expression pattern. Because many features, including structure and transport mechanism, are shared by many ABC transporters, it is worthwhile to evaluate if and to what extent the knowledge on the physiology and pathophysiology of these other transporters may provide useful clues toward understanding the (patho)physiological role of ABCC6 and how its deficiency may be dealt with.
authors.affiliation: Center for Medical Genetics, Ghent University Hospital Ghent, Belgium.
authors.forename: Olivier M
authors.initials: OM
authors.lastname: Vanakker
authors.forename: Mohammad J
authors.initials: MJ
authors.lastname: Hosen
authors.forename: Anne De
authors.initials: AD
authors.lastname: Paepe
keywords: ABC transporters; ABCC6; clinical variability; integrated approach; modifier genes; pseudoxanthoma elasticum; substrate identification; systems biology