Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice

Bottom-current control on sedimentation in the western Bellingshausen Sea, West Antarctica

A set of single channel and multi channel seismic reflection profiles provide insights in the young Cenozoic sedimentation history on the continental rise of the western Bellingshausen Sea west and north of Peter I Island. This area was mainly influenced by the glacial controlled sediment supply from the continental shelf and by bottom current activity. The seismic data show northwards structural altering of a prominent sediment mound from a sediment drift structure into a oppositional orientated large channel-levee complex lying west of an erosional channel. This change indicates a northward decreasing influence of a westward flowing bottom contour current. The topography suggests Peter I Island to be the main feature for the change of the bottom current influence, acting as a barrier for the bottom current and the entrained sediment material. West of Peter I Island the eastward orientated Coriolis force remains as the affecting force which deflects suspended load of the turbidites to the west and leads to a stronger grow of the western channel-levee. Calculated sediment deposition rates based on the seismic data reveal the sediment mound as a remarkable and important sediment depocentre for young Cenozoic glacial transported and contouritic sediment material in the Bellingshausen Sea