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PMID: 10087273 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

PTPmu regulates N-cadherin-dependent neurite outgrowth.

The Journal of cell biology ·Vol. 144 ·No. 6 ·1999-03-22 ·Pages 1323-36

Burden-Gulley SM, Brady-Kalnay SM

Abstract

Cell adhesion is critical to the establishment of proper connections in the nervous system. Some receptor-type protein tyrosine phosphatases (RPTPs) have adhesion molecule-like extracellular segments with intracellular tyrosine phosphatase domains that may transduce signals in response to adhesion. PTPmu is a RPTP that mediates cell aggregation and is expressed at high levels in the nervous system. In this study, we demonstrate that PTPmu promotes neurite outgrowth of retinal ganglion cells when used as a culture substrate. In addition, PTPmu was found in a complex with N-cadherin in retinal cells. To determine the physiological significance of the association between PTPmu and N-cadherin, the expression level and enzymatic activity of PTPmu were perturbed in retinal explant cultures. Downregulation of PTPmu expression through antisense techniques resulted in a significant decrease in neurite outgrowth on an N-cadherin substrate, whereas there was no effect on laminin or L1-dependent neurite outgrowth. The overexpression of a catalytically inactive form of PTPmu significantly decreased neurite outgrowth on N-cadherin. These data indicate that PTPmu specifically regulates signals required for neurites to extend on an N-cadherin substrate, implicating reversible tyrosine phosphorylation in the control of N-cadherin function. Together, these results suggest that PTPmu plays a dual role in the regulation of neurite outgrowth.

MeSH Terms
Animals Axons/physiology Cadherins/physiology Chick Embryo Culture Techniques Gene Expression Neurites/drug effects,physiology,ultrastructure Phosphorylation Protein Tyrosine Phosphatases/genetics,pharmacology,physiology Rats Receptor-Like Protein Tyrosine Phosphatases, Class 2 Receptor-Like Protein Tyrosine Phosphatases, Class 8 Retina/embryology,physiology Retinal Ganglion Cells/drug effects,physiology,ultrastructure Tyrosine/physiology
Chemicals
Cadherins Tyrosine Protein Tyrosine Phosphatases Ptprn protein, rat Receptor-Like Protein Tyrosine Phosphatases, Class 2 Receptor-Like Protein Tyrosine Phosphatases, Class 8
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Burden-Gulley S M
Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4960, USA. smb4@po.cwru.edu
Brady-Kalnay S M
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
Published
1999-03-22
Pages
1323-36
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2150569
Subset
IM
Grants
NEI NIH HHS · 1RO1-EY12251 · United States
NCI NIH HHS · CA-59366-04 · United States
NEI NIH HHS · P30 EY011373 · United States
NEI NIH HHS · R01 EY012251 · United States
NCI NIH HHS · T32 CA059366 · United States
NEI NIH HHS · P0-EY11373 · United States
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