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Fig. 3. Models of HSPG function in cell signaling. (A) HSPG-mediated morphogen
movement along the cell surface by a restricted diffusion mechanism. The
different concentrations of secreted morphogen molecules on the surface of
morphogen-producing and -receiving cells drives the unidirectional
displacement of secreted morphogen molecules from one HS GAG chain to another,
towards more distant receiving cells (indicated by the thin black arrows at
the top). Within the same cell, ligand movement might also be facilitated by
lateral HSPG movement at the cell membrane (indicated by a double-headed
arrow). This model fits well for HSPG-mediated Hh and Dpp movement in the wing
disc (Belenkaya et al., 2004;
Han et al., 2004b). It is also
possible that HSPGs may modulate Wg movement in a similar way, although direct
evidence for this is still lacking. (B) HSPGs might also control cell
signaling by facilitating the dimerization or oligomerization of ligands with
their receptors to initiate cell signaling, as in FGF signalling, where HSPGs
facilitate the formation of the HSPG/FGF/FGFR signaling complexes
(Ornitz, 2000;
Pellegrini, 2001). Dlp may
regulate Hh signaling in a similar way by facilitating Hh-Ptc receptor
interactions in the embryonic epidermis and in cultured cells
(Desbordes and Sanson, 2003;
Lum et al., 2003). (C) Rather
than being required for the formation of an active ligand-receptor
complex(es), HSPGs might alternatively control ligand stability or retention
at the cell surface, through the binding of ligands to HS GAG chains.
Accumulated ligands might thus promote maximal signaling through their
receptors. This model is supported by data on the role of HSPGs in Wg
signaling in the embryonic epidermis
(Hacker et al., 1997;
Lin and Perrimon, 2003;
Pfeiffer et al., 2002).
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