Dual regulation of neuronal morphogenesis by a delta-catenin-cortactin complex and Rho.
Delta-catenin is a neuronal protein that contains 10 Armadillo motifs and binds to the juxtamembrane segment of classical cadherins. We report that delta-catenin interacts with cortactin in a tyrosine phosphorylation-dependent manner. This interaction occurs within a region of the delta-catenin sequence that is also essential for the neurite elongation effects. Src family kinases can phosphorylate delta-catenin and bind to delta-catenin through its polyproline tract. Under conditions when tyrosine phosphorylation is reduced, delta-catenin binds to cortactin and cells extend unbranched primary processes. Conversely, increasing tyrosine phosphorylation disrupts the delta-catenin-cortactin complex. When RhoA is inhibited, delta-catenin enhances the effects of Rho inhibition on branching. We conclude that delta-catenin contributes to setting a balance between neurite elongation and branching in the elaboration of a complex dendritic tree.
Martinez
Maria Cruz
MC
Dept. of Neurology, Brigham and Women's Hospital and Harvard Medical School, Harvard Institute of Medicine, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.
Ochiishi
Tomoyo
T
Majewski
Michael
M
Kosik
Kenneth S
KS
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D051186:Armadillo Domain Proteins; D001921:Brain / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051177:Catenins; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation / Q000502:physiology*; D048429:Cell Size / Q000502:physiology; D051356:Cortactin; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D005333:Fetus; D005822:Genetic Vectors / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure; D016716:PC12 Cells; D010750:Phosphoproteins; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins; D014443:Tyrosine / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism; D000095002:Delta Catenin
D051186:Armadillo Domain Proteins; D051177:Catenins; D015815:Cell Adhesion Molecules; D051356:Cortactin; C495870:Cttn protein, rat; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D011392:Proline; D019061:src-Family Kinases; D020742:rhoA GTP-Binding Protein; D000095002:Delta Catenin