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Fig. 6. Model proposing that the C-lipid mediates long-range signaling of wtShh by
facilitating both multimerization and inactivity. Different N- and C-terminal
lipid-containing Shh multimers are secreted in the ventral forebrain. The
C-terminal lipid-containing multimers exhibit very little
differentiation-inducing activity during short-range signaling. During
long-range signaling, we propose that the C-lipid enables Shh to form L
multimers required for transport, and at the same time maintains Shh in an
inactive state, either by rendering it susceptible to an inhibitor (I) or by
necessitating activation by an activator (X). One possible mechanism of
activation is shown, in which removal of the C-lipid from N+C lipid-containing
L and/or M multimers results in the generation of highly active N-lipid M
multimers.
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