TY - JOUR
T1 - Sorting nexin 31 binds multiple β integrin cytoplasmic domains and regulates β1 integrin surface levels and stability
AU - Tseng, Hui Yuan
AU - Thorausch, Niko
AU - Ziegler, Tilman
AU - Meves, Alexander
AU - Fässler, Reinhard
AU - Böttcher, Ralph T.
N1 - Funding Information:
We thank Dr Roman Nawroth (Technical University of Munich) for providing the RT4 cells and Hildegard Reiter for expert technical assistance. This work was funded by the German Center for Cardiovascular Research and the Deutsche Forschungsgemeinschaft ( SFB 914, project A5 ).
PY - 2014/9/9
Y1 - 2014/9/9
N2 - Trafficking of α5β1 integrin to lysosomes and its subsequent degradation is influenced by ligand occupancy and the binding of SNX17 via its protein 4.1, ezrin, radixin, moesin (FERM) domain to the membrane-distal NPxY motif in the cytoplasmic domain of β1 integrin in early endosomes. Two other sorting nexin (SNX) family members, namely SNX27 and SNX31, share with SNX17 next to their obligate phox domain a FERM domain, which may enable them to bind β integrin tails. Here we report that, in addition to SNX17, SNX31 but not SNX27 binds several β integrin tails in early endosomes in a PI3 (phosphatidylinositide 3)-kinase-dependent manner. Similarly like SNX17, binding of SNX31 with β1 integrin tails in early endosomes occurs between the FERM domain and the membrane-distal NPxY motif in the β1 integrin cytoplasmic domain. Furthermore, expression of SNX31 rescues β1 integrin surface levels and stability in SNX17-depleted cells. In contrast to SNX17, expression of SNX31 is restricted and found highly expressed in bladder and melanoma tissue. Altogether, these results demonstrate that SNX31 is an endosomal regulator of β integrins with a restricted expression pattern.
AB - Trafficking of α5β1 integrin to lysosomes and its subsequent degradation is influenced by ligand occupancy and the binding of SNX17 via its protein 4.1, ezrin, radixin, moesin (FERM) domain to the membrane-distal NPxY motif in the cytoplasmic domain of β1 integrin in early endosomes. Two other sorting nexin (SNX) family members, namely SNX27 and SNX31, share with SNX17 next to their obligate phox domain a FERM domain, which may enable them to bind β integrin tails. Here we report that, in addition to SNX17, SNX31 but not SNX27 binds several β integrin tails in early endosomes in a PI3 (phosphatidylinositide 3)-kinase-dependent manner. Similarly like SNX17, binding of SNX31 with β1 integrin tails in early endosomes occurs between the FERM domain and the membrane-distal NPxY motif in the β1 integrin cytoplasmic domain. Furthermore, expression of SNX31 rescues β1 integrin surface levels and stability in SNX17-depleted cells. In contrast to SNX17, expression of SNX31 is restricted and found highly expressed in bladder and melanoma tissue. Altogether, these results demonstrate that SNX31 is an endosomal regulator of β integrins with a restricted expression pattern.
KW - SNX17
KW - SNX27
KW - integrin trafficking
KW - melanoma
KW - protein turnover
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U2 - 10.1016/j.jmb.2014.07.003
DO - 10.1016/j.jmb.2014.07.003
M3 - Article
C2 - 25020227
AN - SCOPUS:84906217775
SN - 0022-2836
VL - 426
SP - 3180
EP - 3194
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 18
ER -