title: Distinct PTPmu-associated signaling molecules differentially regulate neurite outgrowth on E-, N-, and R-cadherin.
abstract: Classical cadherins play distinct roles in axon growth and guidance in the visual system, however, the signaling pathways they activate remain unclear. Growth cones on each cadherin substrate have a unique morphology suggesting that distinct signals are activated by neurite outgrowth on E-, N-, and R-cadherin. We previously demonstrated that receptor protein tyrosine phosphatase-mu (PTPmu) is required for E- and N-cadherin-dependent neurite outgrowth. In this manuscript, we demonstrate that PTPmu regulates R-cadherin-mediated neurite outgrowth. Furthermore, we evaluated whether known PTPmu-associated signaling proteins, Rac1, Cdc42, IQGAP1 and PKCdelta, regulate neurite outgrowth mediated by these cadherins. While Rac1 activity is required for neurite outgrowth on all three cadherins Cdc42/IQGAP1 are required only for N- and R-cadherin-mediated neurite outgrowth. In addition, we determined that PKC activity is required for E- and R-cadherin-mediated, but not N-cadherin-mediated neurite outgrowth. In summary, distinct PTPmicro-associated signaling proteins are required to promote neurite outgrowth on cadherins.
authors.affiliation: Department of Molecular Biology and Microbiology, Case Western Reserve University, School of Medicine, Cleveland, OH 44106, USA.
authors.forename: Samantha A
authors.initials: SA
authors.lastname: Oblander
authors.forename: Susann M
authors.initials: SM
authors.lastname: Brady-Kalnay
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002642:Chick Embryo; D020439:Growth Cones / Q000378:metabolism* / Q000648:ultrastructure; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure; D055495:Neurogenesis / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2 / Q000235:genetics / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000196:embryology*; D015398:Signal Transduction / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015820:Cadherins; C083970:R-cadherin; D011493:Protein Kinase C; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D020830:rac1 GTP-Binding Protein