scholarly journals Receptor tyrosine phosphatases regulate axon guidance across the midline of the Drosophila embryo

Development ◽  
2000 ◽  
Vol 127 (4) ◽  
pp. 801-812 ◽  
Author(s):  
Q. Sun ◽  
S. Bahri ◽  
A. Schmid ◽  
W. Chia ◽  
K. Zinn
Keyword(s):  
Axon Guidance ◽  
Protein Tyrosine Phosphatases ◽  
Growth Cones ◽  
Drosophila Embryo ◽  
Axonal Pathfinding ◽  
Tyrosine Phosphatases ◽  
Robo Receptors ◽  
Positive Regulators ◽  
Receptor Tyrosine Phosphatases ◽  
Mutant Phenotypes

Neural receptor-linked protein tyrosine phosphatases (RPTPs) are required for guidance of motoneuron and photoreceptor growth cones in Drosophila. These phosphatases have not been implicated in growth cone responses to specific guidance cues, however, so it is unknown which aspects of axonal pathfinding are controlled by their activities. Three RPTPs, known as DLAR, DPTP69D, and DPTP99A, have been genetically characterized thus far. Here we report the isolation of mutations in the fourth neural RPTP, DPTP10D. The analysis of double mutant phenotypes shows that DPTP10D and DPTP69D are necessary for repulsion of growth cones from the midline of the embryonic central nervous system. Repulsion is thought to be triggered by binding of the secreted protein Slit, which is expressed by midline glia, to Roundabout (Robo) receptors on growth cones. Robo repulsion is downregulated by the Commissureless (Comm) protein, allowing axons to cross the midline. Here we show that the Rptp mutations genetically interact with robo, slit and comm. The nature of these interactions suggests that DPTP10D and DPTP69D are positive regulators of Slit/Roundabout repulsive signaling. We also show that elimination of all four neural RPTPs converts most noncrossing longitudinal pathways into commissures that cross the midline, indicating that tyrosine phosphorylation controls the manner in which growth cones respond to midline signals.

scholarly journals Receptor Tyrosine Phosphatases Are Required for Motor Axon Guidance in the Drosophila Embryo

Cell ◽  
1996 ◽  
Vol 84 (4) ◽  
pp. 599-609 ◽  
Author(s):  
Chand J Desai ◽  
Joseph G Gindhart ◽  
Lawrence S.B Goldstein ◽  
Kai Zinn
Keyword(s):  
Axon Guidance ◽  
Motor Axon ◽  
Drosophila Embryo ◽  
Tyrosine Phosphatases ◽  
Receptor Tyrosine Phosphatases

scholarly journals Competition and cooperation among receptor tyrosine phosphatases control motoneuron growth cone guidance in Drosophila

Development ◽  
1997 ◽  
Vol 124 (10) ◽  
pp. 1941-1952 ◽  
Author(s):  
C.J. Desai ◽  
N.X. Krueger ◽  
H. Saito ◽  
K. Zinn
Keyword(s):  
Growth Cone ◽  
Drosophila Embryo ◽  
Tyrosine Phosphatases ◽  
Intermediate Target ◽  
Terminal Arbor ◽  
Cellular Context ◽  
The Common ◽  
Receptor Tyrosine Phosphatases ◽  
Partial Redundancy ◽  
Growth Cone Guidance

The neural receptor tyrosine phosphatases DPTP69D, DPTP99A and DLAR are involved in motor axon guidance in the Drosophila embryo. Here we analyze the requirements for these three phosphatases in growth cone guidance decisions along the ISN and SNb motor pathways. Any one of the three suffices for the progression of ISN pioneer growth cones beyond their first intermediate target in the dorsal muscle field. DLAR or DPTP69D can facilitate outgrowth beyond a second intermediate target, and DLAR is uniquely required for formation of a normal terminal arbor. A different pattern of partial redundancy among the three phosphatases is observed for the SNb pathway. Any one of the three suffices to allow SNb axons to leave the common ISN pathway at the exit junction. When DLAR is not expressed, however, SNb axons sometimes bypass their ventrolateral muscle targets after leaving the common pathway, instead growing out as a separate bundle adjacent to the ISN. This abnormal guidance decision can be completely suppressed by also removing DPTP99A, suggesting that DLAR turns off or counteracts a DPTP99A signal that favors the bypass axon trajectory. Our results show that the relationships among the tyrosine phosphatases are complex and dependent on cellular context. At growth cone choice points along one nerve, two phosphatases cooperate, while along another nerve these same phosphatases can act in opposition to one another.

Complex Genetic Interactions among Four Receptor Tyrosine Phosphatases Regulate Axon Guidance in Drosophila

2001 ◽  
Vol 17 (2) ◽  
pp. 274-291 ◽  
Author(s):  
Qi Sun ◽  
Benno Schindelholz ◽  
Matthias Knirr ◽  
Aloisia Schmid ◽  
Kai Zinn
Keyword(s):  
Axon Guidance ◽  
Genetic Interactions ◽  
Tyrosine Phosphatases ◽  
Receptor Tyrosine Phosphatases

scholarly journals Two receptor tyrosine phosphatases dictate the depth of axonal stabilizing layer in the visual system

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Satoko Hakeda-Suzuki ◽  
Hiroki Takechi ◽  
Hinata Kawamura ◽  
Takashi Suzuki
Keyword(s):  
Visual System ◽  
Molecular Mechanisms ◽  
Protein Tyrosine Phosphatases ◽  
Receptor Protein ◽  
Loss Of Function ◽  
Tyrosine Phosphatases ◽  
Genetic Rescue ◽  
Axonal Connections ◽  
Final Layer ◽  
Receptor Tyrosine Phosphatases

Formation of a functional neuronal network requires not only precise target recognition, but also stabilization of axonal contacts within their appropriate synaptic layers. Little is known about the molecular mechanisms underlying the stabilization of axonal connections after reaching their specifically targeted layers. Here, we show that two receptor protein tyrosine phosphatases (RPTPs), LAR and Ptp69D, act redundantly in photoreceptor afferents to stabilize axonal connections to the specific layers of the Drosophila visual system. Surprisingly, by combining loss-of-function and genetic rescue experiments, we found that the depth of the final layer of stable termination relied primarily on the cumulative amount of LAR and Ptp69D cytoplasmic activity, while specific features of their ectodomains contribute to the choice between two synaptic layers, M3 and M6, in the medulla. These data demonstrate how the combination of overlapping downstream but diversified upstream properties of two RPTPs can shape layer-specific wiring.

SRC binding to the cytoskeleton, triggered by growth cone attachment to laminin, is protein tyrosine phosphatase-dependent

1998 ◽  
Vol 111 (16) ◽  
pp. 2465-2475 ◽  
Author(s):  
S. Helmke ◽  
K. Lohse ◽  
K. Mikule ◽  
M.R. Wood ◽  
K.H. Pfenninger
Keyword(s):  
Phosphatase Activity ◽  
Growth Cone ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Growth Cones ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine ◽  
Adhesion Sites ◽  
Adhesion Site

The interaction of the non-receptor tyrosine kinase, Src, with the cytoskeleton of adhesion sites was studied in nerve growth cones isolated from fetal rat brain. Of particular interest was the role of protein tyrosine phosphatases in the regulation of Src-cytoskeleton binding. Growth cones were found to contain a high level of protein tryrosine phosphatase activity, most of it membrane-associated and forming large, multimeric and wheat germ agglutinin-binding complexes. The receptor tyrosine phosphatase PTPalpha seems to be the most prevalent species among the membrane-associated enzymes. As seen by immunofluorescence, PTPalpha is present throughout the plasmalemma of the growth cone including filopodia, and it forms a punctate pattern consistent with that of integrin beta1. For adhesion site analysis, isolated growth cones were either plated onto the neurite growth substratum, laminin, or kept in suspension. Plating growth cones on laminin triggered an 8-fold increase in Src binding to the adherent cytoskeleton. This effect was blocked completely with the protein tyrosine phosphatase inhibitor, vanadate. Growth cone plating also increased the association with adhesion sites of tyrosine phosphatase activity (14-fold) and of PTPalpha immunoreactivity (6-fold). Vanadate blocked the enzyme activity but not the recruitment of PTPalpha to the adhesion sites. In conjunction with our previous results on growth cones, these data suggest that integrin binding to laminin triggers the recruitment of PTPalpha (and perhaps other protein tyrosine phosphatases) to adhesion sites, resulting in de-phosphorylation of Src's tyr 527. As a result Src unfolds, becomes kinase-active, and its SH2 domain can bind to an adhesion site protein. This implies a critical role for protein tyrosine phosphatase activity in the earliest phases of adhesion site assembly.

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