The protein tyrosine phosphatase PTP1B is required for efficient delivery of N-cadherin to the cell surface.
PTP1B bound to mature N-cadherin promotes the association of beta-catenin into the complex, the stable expression of the complex at cell surface, and cadherin-mediated adhesion. Here we show that PTP1B is also required for N-cadherin precursor trafficking through early stages of the secretory pathway. This function does not require association of PTP1B with the precursor. In PTP1B null cells, the N-cadherin precursor showed higher sensitivity to endoglycosidase H than in cells reconstituted with the wild-type enzyme. It also showed slower kinetics of ER-to-Golgi translocation and processing. Trafficking of the viral stomatitis vesicular glycoprotein, VSV-G, however, revealed no differences between PTP1B null and reconstituted cells. N-cadherin precursor complexes contained similar levels of alpha- and beta-catenin regardless of PTP1B expression. In contrast, the associated p120 catenin (p120) was significantly reduced in absence of PTP1B expression. An N-cadherin precursor construct defective in p120 binding, and expressed in PTP1B reconstituted cells, showed higher sensitivity to endoglycosidase H and slower kinetics of processing than the wild-type precursor. Our results suggest that PTP1B promotes the association of p120 to the N-cadherin precursor, facilitating the trafficking of the complex from the ER to the Golgi complex.
Hernández
Mariana V
MV
Instituto de Investigaciones Biotecnológicas (IIB-INTECH), Universidad de San Martín, 1650 San Martín, Buenos Aires, Argentina.
Wehrendt
Diana P
DP
Arregui
Carlos O
CO
D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D015820:Cadherins / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002645:Chickens; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D007365:Intercellular Junctions / Q000187:drug effects / Q000201:enzymology; D042541:Intracellular Space / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D011485:Protein Binding / Q000187:drug effects; D011498:Protein Precursors / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000737:chemistry / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D015820:Cadherins; D011498:Protein Precursors; D051176:beta Catenin; D020126:Brefeldin A; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1