Postsynaptic shank antagonizes dendrite branching induced by the leucine-rich repeat protein Densin-180.
Leucine-rich repeat and PDZ [postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1] domain proteins such as scribble and Densin-180 have been implicated in the establishment of cell-cell contacts. Here, we show that Densin-180, which has been identified as a constituent of the postsynaptic density in excitatory synapses interacts with the postsynaptic scaffold protein shank (shank1-3). The interaction involves a two-point attachment of the C-terminal region of Densin-180 with the Src homology 3 domain and the N-terminal part of the proline-rich region of shank proteins. The N-terminal leucine-rich repeat region, which is not involved in binding shank, targets Densin-180 to the plasma membrane in transfected cells and to the basolateral membrane of epithelial cells. Nevertheless, coexpression of shank leads to a redirection of Densin-180 into intracellular clusters. In cultured hippocampal neurons, Densin-180 overexpression induces excessive branching of neuronal dendrites, which occurs at the expense of clusters for the postsynaptic marker PSD-95. Coexpression of shank3 abrogates branch formation and targets Densin-180 into postsynaptic clusters instead. Shank blocks binding of delta-catenin but not alphaCaM kinase II to Densin-180; because delta-catenin has been shown to induce branching and neurite formation, our data suggest a mechanism where shank could block the activation of a Densin-180-dependent signaling pathway by delta-catenin.
Quitsch
Arne
A
Institut für Zellbiochemie und klinische Neurobiologie, Universitätskrankenhaus Hamburg-Eppendorf, 20246 Hamburg, Germany.
Berhörster
Kerstin
K
Liew
Chong Wee
CW
Richter
Dietmar
D
Kreienkamp
Hans-Jürgen
HJ
D020816:Amino Acid Motifs; D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D004285:Dogs; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D000090263:Leucine-Rich Repeat Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D012795:Sialoglycoproteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D018909:src Homology Domains
D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C504461:LRRC7 protein, human; D000090263:Leucine-Rich Repeat Proteins; C504463:Lrrc7 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; C033652:postsynaptic density proteins