The mammalian genome encodes 49 proteins that possess a PX (phox-homology) domain, responsible for membrane attachment to organelles of the secretory and endocytic system via binding of phosphoinositide lipids. The PX domain proteins, most of which are classified as SNXs (sorting nexins), constitute an extremely diverse family of molecules that play varied roles in membrane trafficking, cell signalling, membrane remodelling and organelle motility. In the present review, we present an overview of the family, incorporating recent functional and structural insights, and propose an updated classification of the proteins into distinct subfamilies on the basis of these insights. Almost all PX domain proteins bind PtdIns3P and are recruited to early endosomal membranes. Although other specificities and localizations have been reported for a select few family members, the molecular basis for binding to other lipids is still not clear. The PX domain is also emerging as an important protein–protein interaction domain, binding endocytic and exocytic machinery, transmembrane proteins and many other molecules. A comprehensive survey of the molecular interactions governed by PX proteins highlights the functional diversity of the family as trafficking cargo adaptors and membrane-associated scaffolds regulating cell signalling. Finally, we examine the mounting evidence linking PX proteins to different disorders, in particular focusing on their emerging importance in both pathogen invasion and amyloid production in Alzheimer's disease.
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January 2012
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Review Article|
December 14 2011
Insights into the PX (phox-homology) domain and SNX (sorting nexin) protein families: structures, functions and roles in disease
Rohan D. Teasdale;
Rohan D. Teasdale
1Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland 4072, Australia
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Brett M. Collins
Brett M. Collins
1
1Institute for Molecular Bioscience, University of Queensland, St. Lucia, Queensland 4072, Australia
1To whom correspondence should be addressed (email b.collins@imb.uq.edu.au).
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Publisher: Portland Press Ltd
Received:
July 11 2011
Revision Received:
July 26 2011
Accepted:
July 27 2011
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 441 (1): 39–59.
Article history
Received:
July 11 2011
Revision Received:
July 26 2011
Accepted:
July 27 2011
Citation
Rohan D. Teasdale, Brett M. Collins; Insights into the PX (phox-homology) domain and SNX (sorting nexin) protein families: structures, functions and roles in disease. Biochem J 1 January 2012; 441 (1): 39–59. doi: https://doi.org/10.1042/BJ20111226
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