Abstract
The SNX-PXA-RGS-PXC subfamily of sorting nexins (SNXs) belongs to the superfamily of SNX proteins. SNXs are characterized by the presence of a common phox-homology (PX) domain, along with other functional domains that play versatile roles in cellular signaling and membrane trafficking. In addition to the PX domain, the SNX-PXA-RGS-PXC subfamily, except for SNX19, contains a unique RGS (regulators of G protein signaling) domain that serves as GTPase activating proteins (GAPs), which accelerates GTP hydrolysis on the G protein α subunit, resulting in termination of G protein-coupled receptor (GPCR) signaling. Moreover, the PX domain selectively interacts with phosphatidylinositol-3-phosphate and other phosphoinositides found in endosomal membranes, while also associating with various intracellular proteins. Although SNX19 lacks an RGS domain, all members of the SNX-PXA-RGS-PXC subfamily serve as dual regulators of receptor cargo signaling and endosomal trafficking. This review discusses the known and proposed functions of the SNX-PXA-RGS-PXC subfamily and how it participates in receptor signaling (both GPCR and non-GPCR) and endosomal-based membrane trafficking. Furthermore, we discuss the difference of this subfamily of SNXs from other subfamilies, such as SNX-BAR nexins (Bin-Amphiphysin-Rvs) that are associated with retromer or other retrieval complexes for the regulation of receptor signaling and membrane trafficking. Emerging evidence has shown that the dysregulation and malfunction of this subfamily of sorting nexins lead to various pathophysiological processes and disorders, including hypertension.
Highlights
Introduction iationsReceptor-mediated signaling and membrane trafficking processes are intimately interconnected with the endosomes [1]
Emerging evidence has demonstrated that the sorting nexin (SNX)-PXA-RGS-PXC subfamily and their interacting partners are critical regulators for receptor signaling and membrane trafficking
The complex interaction between cellular signaling and endosomal-based membrane trafficking plays an essential role in maintaining cellular homeostasis and versatile functions
Summary
** Fordependent simplicity and the domain structure is not complete for all subfamily processing for amyloid-β number inunclassified the parenthesis the the member proteins of to the. Residues among all of the peptides, one dotSNX19, indicates ganization of SNX-PXA-RGS-PXC All members ofseven this subfamily, except have the weakly conserved amino acid residues, and double dots indicate the well-conserved amino acid residues among all of unique RGS domains, which are aligned with RGS proteins, as shown. Rectifying potassium; GTP, guanosine triphosphate; Mem, intracellular membranes; PI3 kinase, phosphoinositide 3-kinase; PLC, phospholipase C; PM, plasma membrane; Rac, Rac G protein; The PX domain of the SNX-PXA-RGS-PXC subfamily is similar to the PX domains of all other SNX subfamilies, with around 100-130 residues, comprised of three β-strands and three α-helices [8]. The molecular details of these interactions remain to be characterized further
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