[Abstract Title]. - Society for Neuroscience

Support: NSERC
Title: Elucidating a role for CAPON in synaptogenesis
Authors: L. RICHIER 1 , M. O'BRIEN 1 , N. ZINCK 1 , S. KRUEGER 2 , T. PAWSON 4 , *J. P.
FAWCETT 3 ;
1 Pharmacol., 2 Physiol. and Biophysics, 3 Pharmacol. and Surgery, Dalhousie, Halifax, NS,
Canada; 4 Samuel Lunenfeld Res. Inst., Toronto, ON, Canada
Abstract: The synapse is a highly differentiated organelle designed to mediate the transmission
of information between axons and dendrites on target cells. Both the axon and dendrite contain
different complements of proteins that are necessary to give rise to their specialized function.
Recent genetic and biochemical studies have revealed a number of conserved polarity proteins
including Par3 and scribble in synaptic function. To gain insight into the function of scribble in
the synapse we conducted a mass spectrometry screen using scribble as bait to identify novel
interacting proteins. Our screen identified a number of proteins implicated in the synapse
including carboxy-terminal PSD-95/DLG/ZO-1 (PDZ) ligand of nNOS (CAPON), G-protein
coupled receptor interacting protein1 and 2 (Git1,2), p21 kinase activated (PAK) interacting
exchange factor (β-Pix) and p21 activated kinase (PAK). CAPON contains an amino terminal
phosphotyrosine binding (PTB) domain followed by a carboxyl terminal PDZ binding motif. The
PTB domain has been shown to bind synapsin1 and DexRas while the carboxy-terminal PDZ
binding motif has been shown to bind directly to the PDZ domain of nNOS. In our screen we
also identified a novel CAPON splice variant (CAPONLong) that destroys the carboxyl terminal
PDZ binding motif. CAPONLong fails to associate with nNOS suggesting a novel function for
this isoform in the CNS. The association between scribble and CAPON is dependent on the PTB
domain of CAPON and the fourth PDZ domain of scribble. Furthermore, scribble bridges the
association between CAPON and a Git1/β-Pix complex. Overexpression of CAPON in
dissociated hippocampal neurons induces filopodial outgrowth on dendrites. This outgrowth is
dependent on the PTB domain of CAPON. Together these data suggest that CAPON plays an
important role in synaptic development.
Disclosures: L. Richier, None; J.P. Fawcett , None; M. O'Brien, None; N. Zinck, None; S.
Krueger, None; T. Pawson, None.
Poster
231. Dendrite Growth and Branching: Signaling
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 231.5/B18
Topic: A.04.i. Dendritic growth and branching