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© The Rockefeller University Press, 0021-9525/1999//1323 $5.00
The Journal of Cell Biology, Volume 144, Number 6, , 1999 1323-1336

PTPµ Regulates N-Cadherin–dependent Neurite Outgrowth

Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106-4960

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. PTPµ is a RPTP that mediates cell aggregation and is expressed at high levels in the nervous system. In this study, we demonstrate that PTPµ promotes neurite outgrowth of retinal ganglion cells when used as a culture substrate. In addition, PTPµ was found in a complex with N-cadherin in retinal cells. To determine the physiological significance of the association between PTPµ and N-cadherin, the expression level and enzymatic activity of PTPµ were perturbed in retinal explant cultures. Downregulation of PTPµ 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 PTPµ significantly decreased neurite outgrowth on N-cadherin. These data indicate that PTPµ 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 PTPµ plays a dual role in the regulation of neurite outgrowth.

Key Words: neurite outgrowth • protein tyrosine phosphatase • cadherin • cell adhesion • retina

Abbreviations used in this paper: CAM, cell adhesion molecule; GFP, green fluorescent protein; RGC, retinal ganglion cell; RPTP, receptor-type protein tyrosine phosphatase.

A number of individuals provided assistance with this study, and their efforts were greatly appreciated. These include Dr. Leif Stordal, who generated the retroviral plasmids used for the antisense experiments, and Tracy Mourton and Ferdouse Sartawi, who provided expert technical assistance. The many contributions of Dr. Vance Lemmon throughout the course of this study are greatly appreciated. In addition, we thank Drs. Lloyd Culp, Lynn Landmesser, Gary Landreth, Vance Lemmon, and Robert Miller for helpful comments on the manuscript.

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