Subcellular sorting of the G-protein coupled mouse somatostatin receptor 5 by a network of PDZ-domain containing proteins

PSD-95/discs large/ZO-1 (PDZ) domain proteins integrate many G-protein coupled receptors (GPCRs) into membrane associated signalling complexes. Additional PDZ proteins are involved in intracellular receptor trafficking. We show that three PDZ proteins (SNX27, PIST and NHERF1/3) regulate the mouse so...

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Bibliographic Details
Published in:PloS one 2014-02, Vol.9 (2), p.e88529-e88529
Main Authors: Bauch, Carola, Koliwer, Judith, Buck, Friedrich, Hönck, Hans-Hinrich, Kreienkamp, Hans-Jürgen
Format: Article
Language:English
Subjects:
Amino Acid Motifs
Animals
Biology
Biotinylation
Carrier Proteins - metabolism
Cell Membrane - metabolism
Compartments
Cystic fibrosis
Degradation
Endocytosis
Endosomes - metabolism
G protein-coupled receptors
Gene Expression Regulation
Golgi apparatus
Golgi Apparatus - metabolism
HEK293 Cells
Humans
Internalization
Intracellular signalling
Kinases
Ligands
Localization
Membrane proteins
Membranes
Mice
PDZ Domains
Phosphoproteins - metabolism
Plasma
Postsynaptic density proteins
Protein Transport
Proteins
Receptors
Receptors, Somatostatin - metabolism
Sodium-Hydrogen Exchangers - metabolism
Somatostatin
Somatostatin receptors
Sorting Nexins - metabolism
Zonula occludens-1 protein
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Summary:PSD-95/discs large/ZO-1 (PDZ) domain proteins integrate many G-protein coupled receptors (GPCRs) into membrane associated signalling complexes. Additional PDZ proteins are involved in intracellular receptor trafficking. We show that three PDZ proteins (SNX27, PIST and NHERF1/3) regulate the mouse somatostatin receptor subtype 5 (SSTR5). Whereas the PDZ ligand motif of SSTR5 is not necessary for plasma membrane targeting or internalization, it protects the SSTR5 from postendocytic degradation. Under conditions of lysosomal inhibition, recycling of the SSTR5 to the plasma membrane does not depend on the PDZ ligand. However, recycling of the wild type receptor carrying the PDZ binding motif depends on SNX27 which interacts and colocalizes with the receptor in endosomal compartments. PIST, implicated in lysosomal targeting of some membrane proteins, does not lead to degradation of the SSTR5. Instead, overexpressed PIST retains the SSTR5 at the Golgi. NHERF family members release SSTR5 from retention by PIST, allowing for plasma membrane insertion. Our data suggest that PDZ proteins act sequentially on the GPCR at different stages of its subcellular trafficking.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0088529