TITLE:
Ligand-induced dimerization of syndecan-3 at the cell surface
AUTHORS:
Evgeny Kulesskiy, Sarka Tumova, Heikki Rauvala
KEYWORDS:
Syndecan-3; Dimerization; HB-GAM; Pleiotrophin; BRET; FRET
JOURNAL NAME:
Advances in Bioscience and Biotechnology,
Vol.4 No.6A,
June
20,
2013
ABSTRACT:
Syndecan-3 (N-syndecan) is a transmembrane heparan
sulfate proteoglycan abundantly expressed in developing brain. In addition to
acting as a coreceptor, syndecan-3 acts as a signaling receptor upon binding
of its ligand HB-GAM (heparin-binding growth-associated molecule;
pleiotrophin), which activates the cortactin-src kinase signaling pathway.
This leads to rapid neurite extension in neuronal cells, which makes syndecan-3
as an interesting transmembrane receptor in neuronal development and
regeneration. However, little is known about the signaling mechanism of
syndecan-3. Here we have analyzed formation of ligand-N-syndecan signaling complexes at the cell surface using fluorescence resonance energy transfer (FRET)
and bioluminescence resonance energy transfer (BRET). We show that ligand
binding leads to dimerization of syndecan-3 at the cell surface. The dimerized
syndecan-3 colocalizes with actin in the filopodia of cells. Several amino acid
residues (K383, G392 and G396) in the transmembrane domain are shown to be
important for the ligand-induced dimerization, whereas the cytosolic domain is
not required for the dimerization.