Insights into the PX (phox-homology) domain and SNX (sorting nexin) protein families: structures, functions and roles in disease

Teasdale, Rohan D. and Collins, Brett M. (2012) Insights into the PX (phox-homology) domain and SNX (sorting nexin) protein families: structures, functions and roles in disease. Biochemical Journal, 441 Part 1: 39-59. doi:10.1042/BJ20111226


Author Teasdale, Rohan D.
Collins, Brett M.
Title Insights into the PX (phox-homology) domain and SNX (sorting nexin) protein families: structures, functions and roles in disease
Journal name Biochemical Journal   Check publisher's open access policy
ISSN 0264-6021
1470-8728
Publication date 2012-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1042/BJ20111226
Volume 441
Issue Part 1
Start page 39
End page 59
Total pages 21
Place of publication London, United Kingdom
Publisher Portland Press
Collection year 2012
Language eng
Abstract 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.
Keyword Alzheimer's disease
Endosome
Phosphoinositide
Phox-homology domain (PX domain)
Retromer
Sorting nexin (SNX)
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online 14 December 2011

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Biomedical Sciences Publications
 
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Created: Tue, 20 Sep 2011, 22:36:32 EST by Brett Collins on behalf of School of Biomedical Sciences