September 5, 2008;
A protein scaffold plays matchmaker for chordin.
In this issue, Inomata et al. (2008) report that the scaffold protein Olfactomedin 1 (ONT1
) recruits the Tolloid
proteases to their substrate Chordin
, an antagonist of bone
morphogenetic proteins (BMPs), during development of the frog embryo
. Consequently, ONT1
expression in the organizer
of the late gastrula
stabilizes the gradient of BMP signaling that is essential for dorsoventral patterning.
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Tuning BMP Signaling
Bone morphogenetic proteins (BMPs) are essential regulators of vertebrate development. Chordin, Follistatin, Noggin, Xnr3, and Cerberus are BMP antagonists that are important for tuning BMP signaling and are expressed in the organizer on the dorsal side of the embryo. Chordin is itself regulated through degradation by the Tolloid proteases that are brought into its proximity by the scaffold protein ONT1 (Inomata et al., 2008). The BMP antagonist twisted gastrulation (Tsg in Xenopus and Drosophila and twsg1 in mice) cooperates with Chordin to block BMP activity and is ubiquitously expressed. Among the BMPs, antidorsalizing morphogenetic protein (ADMP) is specific to the dorsal side of the embryo and is induced by low BMP concentrations, whereas the other BMPs are still present in the organizer but are more generally expressed. ONT1 is expressed ubiquitously at first but becomes progressively localized to the organizer region; Tolloid-related genes (Tll) are ubiquitously expressed. BMP4 is localized specifically to the ventral side at the mid-gastrula stage. Tsg also interacts with Chordin and BMP complexes to promote Chordin degradation and to liberate BMP, although in Xenopus the BMP antagonist role illustrated for the dorsal side predominates. The negative feedback components of BMP signaling include Sizzled, which binds to Xolloid-related proteases and prevents Chordin degradation. BAMBI is a decoy BMP receptor expressed in response to BMPs.
Inomata, Robust stability of the embryonic axial pattern requires a secreted scaffold for chordin degradation. 2008, Pubmed