scholarly journals PTPμ Regulates N-Cadherin–dependent Neurite Outgrowth

1999 ◽  
Vol 144 (6) ◽  
pp. 1323-1336 ◽  
Author(s):  
Susan M. Burden-Gulley ◽  
Susann M. Brady-Kalnay

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.

2000 ◽  
Vol 20 (20) ◽  
pp. 7706-7715 ◽  
Author(s):  
S. Harroch ◽  
M. Palmeri ◽  
J. Rosenbluth ◽  
A. Custer ◽  
M. Okigaki ◽  
...  

ABSTRACT The development of neurons and glia is governed by a multitude of extracellular signals that control protein tyrosine phosphorylation, a process regulated by the action of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Receptor PTPβ (RPTPβ; also known as PTPζ) is expressed predominantly in the nervous system and exhibits structural features common to cell adhesion proteins, suggesting that this phosphatase participates in cell-cell communication. It has been proposed that the three isoforms of RPTPβ play a role in regulation of neuronal migration, neurite outgrowth, and gliogenesis. To investigate the biological functions of this PTP, we have generated mice deficient in RPTPβ. RPTPβ-deficient mice are viable, are fertile, and showed no gross anatomical alterations in the nervous system or other organs. In contrast to results of in vitro experiments, our study demonstrates that RPTPβ is not essential for neurite outgrowth and node formation in mice. The ultrastructure of nerves of the central nervous system in RPTPβ-deficient mice suggests a fragility of myelin. However, conduction velocity was not altered in RPTPβ-deficient mice. The normal development of neurons and glia in RPTPβ-deficient mice demonstrates that RPTPβ function is not necessary for these processes in vivo or that loss of RPTPβ can be compensated for by other PTPs expressed in the nervous system.


2002 ◽  
Vol 21 (2) ◽  
pp. 301-311 ◽  
Author(s):  
B LORBER ◽  
M BERRY ◽  
A LOGAN ◽  
D TONGE

Author(s):  
Paul J. May ◽  
Anton Reiner ◽  
Paul D. Gamlin

The functions of the eye are regulated by and dependent upon the autonomic nervous system. The parasympathetic nervous system controls constriction of the iris and accommodation of the lens via a pathway with preganglionic motor neurons in the Edinger-Westphal nucleus and postganglionic motor neurons in the ciliary ganglion. The parasympathetic nervous system regulates choroidal blood flow and the production of aqueous humor through a pathway with preganglionic motor neurons in the superior salivatory nucleus and postganglionic motor neurons in the pterygopalatine (sphenopalatine) ganglion. The sympathetic nervous system controls dilation of the iris and may modulate the outflow of aqueous humor from the eye. The sympathetic preganglionic motor neurons lie in the intermediolateral cell column at the first level of the thoracic cord, and the postganglionic motor neurons are found in the superior cervical ganglion. The central pathways controlling different autonomic functions in the eye are found in a variety of locations within the central nervous system. The reflex response of the iris to changes in luminance levels begins with melanopsin-containing retinal ganglion cells in the retina that project to the olivary pretectal nucleus. This nucleus then projects upon the Edinger-Westphal preganglionic motoneurons. The dark response that produces maximal pupillary dilation involves the sympathetic pathways to the iris. Pupil size is also regulated by many other factors, but the pathways to the parasympathetic and sympathetic preganglionic motoneurons that underlie this are not well understood. Lens accommodation is controlled by premotor neurons located in the supraoculomotor area. These also regulate the pupil, and control vergence angle by modulating the activity of medial rectus, and presumably lateral rectus, motoneurons. Pathways from the frontal eye fields and cerebellum help regulate their activity. Blood flow in the choroid is regulated with respect to systemic blood pressure through pathways through the nucleus of the tractus solitarius. It is also regulated with respect to luminance levels, which likely involves the suprachiasmatic nucleus, which receives inputs from melanopsin-containing retinal ganglion cells, and other areas of the hypothalamus that project upon the parasympathetic preganglionic neurons of the superior salivatory nucleus that mediate choroidal vasodilation.


2019 ◽  
Vol 8 (7) ◽  
pp. 936 ◽  
Author(s):  
Faria ◽  
Andrade ◽  
Reijm ◽  
Spaander ◽  
de Maat ◽  
...  

Venous thromboembolism (VTE) is one of the most common causes of cancer related mortality. It has been speculated that hypercoagulation in cancer patients is triggered by direct or indirect contact of platelets with tumor cells, however the underlying molecular mechanisms involved are currently unknown. Unraveling these mechanisms may provide potential avenues for preventing platelet-tumor cell aggregation. Here, we investigated the role of protein tyrosine phosphatases in the functionality of platelets in both healthy individuals and patients with gastrointestinal cancer, and determined their use as a target to inhibit platelet hyperactivity. This is the first study to demonstrate that platelet agonists selectively activate low molecular weight protein tyrosine phosphatase (LMWPTP) and PTP1B, resulting in activation of Src, a tyrosine kinase known to contribute to several platelet functions. Furthermore, we demonstrate that these phosphatases are a target for 3-bromopyruvate (3-BP), a lactic acid analog currently investigated for its use in the treatment of various metabolic tumors. Our data indicate that 3-BP reduces Src activity, platelet aggregation, expression of platelet activation makers and platelet-tumor cell interaction. Thus, in addition to its anti-carcinogenic effects, 3-BP may also be effective in preventing platelet-tumor cell aggregationin cancer patients and therefore may reduce cancer mortality by limiting VTE in patients.


2000 ◽  
Vol 93 (2) ◽  
pp. 275-278 ◽  
Author(s):  
Grant A. Robinson ◽  
Roger D. Madison

Object. The goal of this study was to examine whether the method of attachment of a peripheral nerve graft would have an effect on retinal ganglion cell (RGC) regeneration.Methods. The number of adult rat RGCs with regrown axons in a peripheral nerve graft was compared under two grafting conditions: 1) attachment of the graft to the optic nerve stump made using a suture; and 2) attachment made using fibrin glue. Counts of RGCs retrogradely labeled with FluoroGold from the grafts 1 month after attachment revealed approximately seven times the number of RGCs in the fibrin-glue group compared with the suture group.Conclusions. The use of fibrin glue may be a useful tool for enhancing the regrowth of central nervous system neuron axons into peripheral nervous system grafts.


2016 ◽  
Vol 215 (2) ◽  
pp. 147-149 ◽  
Author(s):  
Jeremy N. Kay

Newborn neuron radial migration is a key force shaping the nervous system. In this issue, Icha et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201604095) use zebrafish retinal ganglion cells as a model to investigate the cell biological basis of radial migration and the consequences for retinal histogenesis when migration is impaired.


2005 ◽  
Vol 46 (3) ◽  
pp. 933 ◽  
Author(s):  
Wolf A. Lagre`ze ◽  
Amelie Pielen ◽  
Ruth Steingart ◽  
Gu¨nther Schlunck ◽  
Hans-Dieter Hofmann ◽  
...  

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