Receptor-like Protein-tyrosine Phosphatase α Enhances Cell Surface Expression of Neural Adhesion Molecule NB-3

Yen Ling Jessie Tan,Zhi-Cheng Xiao,Catherine J. Pallen,Jianghong Liu,Haihong Ye,Tian Zhao

doi:10.1074/jbc.m110.214080

Abstract

Neural adhesion molecule NB-3 plays an important role in the apical dendrite development of layer V pyramidal neurons in the visual cortex, and receptor-like protein-tyrosine phosphatase α (PTPα) mediates NB-3 signaling in this process. Here we investigated the role of PTPα in regulating cell surface expression of NB-3. We found that cortical neurons from PTPα knock-out mice exhibited a lower level of NB-3 at the cell surface. When expressed in COS1 cells, NB-3 was enriched in the Golgi apparatus with a low level of cell surface expression. However, co-expression of PTPα increased the cell surface distribution of NB-3. Further analysis showed that PTPα facilitated Golgi exit of NB-3 and stabilized NB-3 protein at the cell surface by preventing its release from the plasma membrane. The extracellular region of PTPα but not its catalytic activity is necessary for its effect on NB-3 expression. Thus, the PTPα-mediated increase of NB-3 level at the cell surface represents a novel function of PTPα in NB-3 signaling in neural development.

Highlights

Protein-tyrosine phosphatase ␣ (PTP␣)4 is a receptor-like protein phosphatase with two cytoplasmic protein-tyrosine phosphatase domains (D1 and D2) and a relatively short and highly glycosylated extracellular domain
PTP␣ Affects NB-3 Cell Surface Expression in Cultured Mouse Cortical Neurons—In search of proteins that enhance cell surface expression of NB-3, we found that PTP␣, which interacts with and mediates signaling of NB-3 [25], modulates its cell surface expression in neurons
When cell surface NB-3 was clustered and stained using a mouse anti-NB-3 antibody, Ptp␣Ϫ/Ϫ neurons exhibited fewer clusters with lower signal intensity (Fig. 1E). These observations indicate that PTP␣ positively regulates NB-3 cell surface expression in neurons and led us to investigate whether PTP␣ itself enhances NB-3 cell surface expression and the possible mechanism

Summary

Introduction

Protein-tyrosine phosphatase ␣ (PTP␣)4 is a receptor-like protein phosphatase with two cytoplasmic protein-tyrosine phosphatase domains (D1 and D2) and a relatively short and highly glycosylated extracellular domain. The low level of NB-3-Myc surface expression in COS1 cells could result from either its intracellular retention in the endoplasmic reticulum (ER) or Golgi apparatus during synthesis, its intense degradation in lysosomes, or cleavage of its GPI link at the cell surface and subsequent release from the cell membrane.

Results

Conclusion