A delta-catenin signaling pathway leading to dendritic protrusions.
Delta-catenin is a synaptic adherens junction protein pivotally positioned to serve as a signaling sensor and integrator. Expression of delta-catenin induces filopodia-like protrusions in neurons. Here we show that the small GTPases of the Rho family act coordinately as downstream effectors of delta-catenin. A dominant negative Rac prevented delta-catenin-induced protrusions, and Cdc42 activity was dramatically increased by delta-catenin expression. A kinase dead LIMK (LIM kinase) and a mutant Cofilin also prevented delta-catenin-induced protrusions. To link the effects of delta-catenin to a physiological pathway, we noted that (S)-3,5-dihydroxyphenylglycine (DHPG) activation of metabotropic glutamate receptors induced dendritic protrusions that are very similar to those induced by delta-catenin. Furthermore, delta-catenin RNA-mediated interference can block the induction of dendritic protrusions by DHPG. Interestingly, DHPG dissociated PSD-95 and N-cadherin from the delta-catenin complex, increased the association of delta-catenin with Cortactin, and induced the phosphorylation of delta-catenin within the sites that bind to these protein partners.
Abu-Elneel
Kawther
K
Neuroscience Research Institute, and Department of Molecular Cellular and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
Ochiishi
Tomoyo
T
Medina
Miguel
M
Remedi
Monica
M
Gastaldi
Laura
L
Caceres
Alfredo
A
Kosik
Kenneth S
KS
D000818:Animals; D015820:Cadherins / Q000737:chemistry; D051177:Catenins; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry; D008565:Membrane Proteins / Q000737:chemistry; D008954:Models, Biological; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000378:metabolism; D015398:Signal Transduction; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D000095002:Delta Catenin
D015820:Cadherins; D051177:Catenins; D015815:Cell Adhesion Molecules; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D010750:Phosphoproteins; D017470:Receptors, Glutamate; D020764:cdc42 GTP-Binding Protein; D000095002:Delta Catenin