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Gene Review

Lar  -  Leukocyte-antigen-related-like

Drosophila melanogaster

Synonyms: CG10443, DLAR, DLar, Dlar, Dmel\CG10443, ...
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Disease relevance of Lar

  • The leukocyte common antigen-related (LAR) receptor is known to be present in rodent dorsal root ganglion (DRG) neurons; therefore, the well established model of postcrush sciatic nerve regeneration was used to test the hypothesis that LAR is required for neurite outgrowth in the adult mammalian nervous system [1].

High impact information on Lar


Biological context of Lar

  • To understand the regulation of cell proliferation by tyrosine phosphorylation, characterization of protein tyrosine phosphatases (PTPase; protein-tyrosine-phosphate phosphohydrolase, EC is essential [5].
  • By using consensus sequence probes, two additional receptor-linked PTPase genes, DLAR and DPTP, were isolated from Drosophila melanogaster [5].
  • This phenotype is suppressed in Dlar Ptp52F double mutants, indicating that DPTP52F and DLAR interact competitively in regulating CNS axon guidance decisions [6].
  • We show that Lar acts somatically early in oogenesis, during follicle formation, and postulate that it functions in germarium intercyst cells that are required for polar cell specification and differentiation [7].
  • Actin filaments in the basal follicle cell domain normally become polarized during stage 6 around the anterior-posterior axis defined by the polar cells, but mutations in Lar frequently disrupt polar cell differentiation and actin polarization [7].

Anatomical context of Lar

  • Here, we examine the synaptic function of the receptor protein tyrosine phosphatase (RPTP), Dlar, and an associated intracellular protein, Dliprin-alpha, at the Drosophila larval neuromuscular junction [3].
  • Target selection decisions of the R1-R6 subset of photoreceptor axons have been found to be influenced by the nuclear factors Brakeless and Runt, and target selection decisions of the R7 subset of axons have been found to require the cell-surface proteins Ptp69d, Lar and N-cadherin [8].
  • We have identified mutations in the receptor-like transmembrane tyrosine phosphatase Lar that disorganize follicle formation, block egg chamber elongation and disrupt Oskar localization, which is an indicator of oocyte anterior-posterior polarity [7].
  • The Lar-interacting domain of Trio is constitutively tyrosine-phosphorylated when expressed in COS-7 cells and was highly phosphorylated when it was co-transfected with FAK [9].
  • The neural receptor tyrosine phosphatases DPTP69D, DPTP99A and DLAR are involved in motor axon guidance in the Drosophila embryo [10].

Other interactions of Lar

  • Like mutations in the protein tyrosine phosphatase gene Dlar, strong Ptp69D alleles cause the ISNb nerve to bypass its muscle targets [11].
  • However, unlike N-cadherin, neither Liprin-alpha nor LAR is required postsynaptically for R cells to project to their correct targets [12].
  • Here, we describe the identification and characterization of the Drosophila counterpart of Trio, a guanine nucleotide exchange factor (GEF) that associates with the receptor phosphatase LAR and regulates GTPase activation in vertebrate cells [13].
  • We now demonstrate that the Drosophila Abl tyrosine kinase functions in the intersegmental nerve b (ISNb) motor choice point pathway as an antagonist of the RPTP Dlar [14].
  • 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 [10].

Analytical, diagnostic and therapeutic context of Lar

  • Electron microscopy analysis revealed a significant twofold reduction in the density of regenerating unmyelinated fibers in LAR-/- nerves distal to the crush site [1].
  • Two weeks after nerve crush, morphological analysis of distal nerve segments in LAR-deficient transgenic mice demonstrated significantly decreased densities of myelinated fibers, decreased axonal areas, and increased myelin/axon area ratios compared with littermate controls [1].


  1. The leukocyte common antigen-related protein tyrosine phosphatase receptor regulates regenerative neurite outgrowth in vivo. Xie, Y., Yeo, T.T., Zhang, C., Yang, T., Tisi, M.A., Massa, S.M., Longo, F.M. J. Neurosci. (2001) [Pubmed]
  2. The transmembrane tyrosine phosphatase DLAR controls motor axon guidance in Drosophila. Krueger, N.X., Van Vactor, D., Wan, H.I., Gelbart, W.M., Goodman, C.S., Saito, H. Cell (1996) [Pubmed]
  3. Drosophila liprin-alpha and the receptor phosphatase Dlar control synapse morphogenesis. Kaufmann, N., DeProto, J., Ranjan, R., Wan, H., Van Vactor, D. Neuron (2002) [Pubmed]
  4. Drosophila LAR regulates R1-R6 and R7 target specificity in the visual system. Clandinin, T.R., Lee, C.H., Herman, T., Lee, R.C., Yang, A.Y., Ovasapyan, S., Zipursky, S.L. Neuron (2001) [Pubmed]
  5. A family of receptor-linked protein tyrosine phosphatases in humans and Drosophila. Streuli, M., Krueger, N.X., Tsai, A.Y., Saito, H. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  6. Regulation of CNS and motor axon guidance in Drosophila by the receptor tyrosine phosphatase DPTP52F. Schindelholz, B., Knirr, M., Warrior, R., Zinn, K. Development (2001) [Pubmed]
  7. The receptor-like tyrosine phosphatase lar is required for epithelial planar polarity and for axis determination within drosophila ovarian follicles. Frydman, H.M., Spradling, A.C. Development (2001) [Pubmed]
  8. Axon targeting in the Drosophila visual system. Tayler, T.D., Garrity, P.A. Curr. Opin. Neurobiol. (2003) [Pubmed]
  9. Signaling between focal adhesion kinase and trio. Medley, Q.G., Buchbinder, E.G., Tachibana, K., Ngo, H., Serra-Pagès, C., Streuli, M. J. Biol. Chem. (2003) [Pubmed]
  10. Competition and cooperation among receptor tyrosine phosphatases control motoneuron growth cone guidance in Drosophila. Desai, C.J., Krueger, N.X., Saito, H., Zinn, K. Development (1997) [Pubmed]
  11. The neural receptor protein tyrosine phosphatase DPTP69D is required during periods of axon outgrowth in Drosophila. Desai, C., Purdy, J. Genetics (2003) [Pubmed]
  12. Liprin-alpha is required for photoreceptor target selection in Drosophila. Choe, K.M., Prakash, S., Bright, A., Clandinin, T.R. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  13. The guanine nucleotide exchange factor trio mediates axonal development in the Drosophila embryo. Bateman, J., Shu, H., Van Vactor, D. Neuron (2000) [Pubmed]
  14. The tyrosine kinase Abl and its substrate enabled collaborate with the receptor phosphatase Dlar to control motor axon guidance. Wills, Z., Bateman, J., Korey, C.A., Comer, A., Van Vactor, D. Neuron (1999) [Pubmed]
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