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 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 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 Homophilic interactions mediated by receptor tyrosine phosphatases μ and κ. A critical role for the novel extracellular MAM domain.

1995 ◽  
Vol 270 (41) ◽  
pp. 24621
Author(s):  
Gerben C.M. Zondag ◽  
Gregory M. Koningstein ◽  
Ying-Ping Jiang ◽  
Jan Sap ◽  
Wouter H. Moolenaar ◽  
...  
Keyword(s):  
Critical Role ◽  
The Novel ◽  
Tyrosine Phosphatases ◽  
Receptor Tyrosine Phosphatases

The Beat generation: a multigene family encoding IgSF proteins related to the Beat axon guidance molecule in Drosophila

Development ◽  
2001 ◽  
Vol 128 (22) ◽  
pp. 4545-4552 ◽  
Author(s):  
G. C. Teg Pipes ◽  
Qing Lin ◽  
Stephanie E. Riley ◽  
Corey S. Goodman
Keyword(s):  
Axon Guidance ◽  
Specific Growth ◽  
Growth Cones ◽  
Beat Generation ◽  
Genetic Screen ◽  
Genetic Interactions ◽  
Membrane Bound ◽  
Adhesive Factor ◽  
Axon Guidance Molecule ◽  
Guidance Molecule

A previous genetic screen led to the identification of the beaten path (beat Ia) gene in Drosophila. Beat Ia contains two immunoglobulin (Ig) domains and appears to function as an anti-adhesive factor secreted by specific growth cones to promote axon defasciculation. We identify a family of 14 beat-like genes in Drosophila. In contrast to beat Ia, four novel Beat-family genes encode membrane-bound proteins. Moreover, mutations in each gene lead to much more subtle guidance phenotypes than observed in beat Ia. Genetic interactions between beat Ic and beat Ia reveal complementary functions. Our data suggest a model whereby Beat Ic (and perhaps other membrane-bound family members) functions in a pro-adhesive fashion to regulate fasciculation, while Beat Ia (the original secreted Beat) functions in an anti-adhesive fashion to regulate defasciculation.

scholarly journals Homophilic Interactions Mediated by Receptor Tyrosine Phosphatases μ and κ. A CRITICAL ROLE FOR THE NOVEL EXTRACELLULAR MAM DOMAIN

1995 ◽  
Vol 270 (24) ◽  
pp. 14247-14250 ◽  
Author(s):  
Gerben C. M. Zondag ◽  
Gregory M. Koningstein ◽  
Ying-Ping Jiang ◽  
Jan Sap ◽  
Wouter H. Moolenaar ◽  
...  
Keyword(s):  
Critical Role ◽  
The Novel ◽  
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.

scholarly journals LAR Receptor Tyrosine Phosphatases and HSPGs Guide Peripheral Sensory Axons to the Skin

2012 ◽  
Vol 22 (5) ◽  
pp. 373-382 ◽  
Author(s):  
Fang Wang ◽  
Sean N. Wolfson ◽  
Arash Gharib ◽  
Alvaro Sagasti
Keyword(s):  
Tyrosine Phosphatases ◽  
Sensory Axons ◽  
Receptor Tyrosine Phosphatases ◽  
Peripheral Sensory

scholarly journals Identification of a carbonic anhydrase-like domain in the extracellular region of RPTP gamma defines a new subfamily of receptor tyrosine phosphatases.

1993 ◽  
Vol 13 (3) ◽  
pp. 1497-1506 ◽  
Author(s):  
G Barnea ◽  
O Silvennoinen ◽  
B Shaanan ◽  
A M Honegger ◽  
P D Canoll ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Transmembrane Domain ◽  
Tyrosine Phosphatase ◽  
Extracellular Domain ◽  
Suppressor Gene ◽  
Tyrosine Phosphatases ◽  
Candidate Tumor Suppressor Gene ◽  
Extracellular Region ◽  
Receptor Tyrosine Phosphatases

The tyrosine phosphatase RPTP gamma is a candidate tumor suppressor gene since it is located on human chromosome 3p14.2-p21 in a region frequently deleted in certain types of renal and lung carcinomas. In order to evaluate its oncogenic potential and to explore its normal in vivo functions, we have isolated cDNAs and deduced the complete sequences of both human and murine RPTP gamma. The murine RPTP gamma gene has been localized to chromosome 14 to a region syntenic to the location of the human gene. Northern (RNA) blot analysis reveals the presence of two major transcripts of 5.5 and 8.5 kb in a variety of murine tissues. In situ hybridization analysis reveals that RPTP gamma mRNA is expressed in specific regions of the brain and that the localization of RPTP gamma changes during brain development. RPTP gamma is composed of a putative extracellular domain, a single transmembrane domain, and a cytoplasmic portion with two tandem catalytic tyrosine phosphatase domains. The extracellular domain contains a stretch of 266 amino acids with striking homology to the zinc-containing enzyme carbonic anhydrase (CAH), indicating that RPTP gamma and RPTP beta (HPTP zeta) represent a subfamily of receptor tyrosine phosphatases. We have constructed a model for the CAH-like domain of RPTP gamma based upon the crystal structure of CAH. It appears that 11 of the 19 residues that form the active site of CAH are conserved in RPTP gamma. Yet only one of the three His residues that ligate the zinc atom and are required for catalytic activity is conserved. On the basis of this model we propose that the CAH-like domain of RPTP gamma may have a function other than catalysis of hydration of metabolic CO2.

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