Distinct PTPmu-associated signaling molecules differentially regulate neurite outgrowth on E-, N-, and R-cadherin

• Published in: Molecular and cellular neuroscience Vol. 44; no. 1; pp. 78 - 93
• Main Authors: Oblander, Samantha A., Brady-Kalnay, Susann M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2010
• Subjects: Animals; Axon guidance; Cadherin; Cadherins - genetics; Cadherins - metabolism; Cell Differentiation - physiology; Cells, Cultured; Cell–cell adhesion; Chick; Chick Embryo; Growth Cones - metabolism; Growth Cones - ultrastructure; Neurite outgrowth; Neurites - metabolism; Neurites - ultrastructure; Neurogenesis - genetics; Protein Kinase C - genetics; Protein Kinase C - metabolism; Protein tyrosine phosphatase; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - metabolism; Receptor-Like Protein Tyrosine Phosphatases, Class 2 - genetics; Receptor-Like Protein Tyrosine Phosphatases, Class 2 - metabolism; Retina; Retina - cytology; Retina - embryology; Signal Transduction - physiology; Protein tyrosine phosphatase; Retina; Cadherin; Axon guidance; Chick; Neurite outgrowth; Cell–cell adhesion
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2010.02.005

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 PKCδ, 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 PTPµ-associated signaling proteins are required to promote neurite outgrowth on cadherins.