Title : N-glycosylation at the
SynCAM (
synaptic cell adhesion molecule ) immunoglobulin interface modulates synaptic adhesion
Abstract :
- Select adhesion molecules connect pre- and postsynaptic membranes and organize developing synapses
- The regulation of these trans-synaptic interactions is an important neurobiological question
- We have previously shown that the synaptic cell adhesion molecules (SynCAMs) 1 and 2 engage in homo- and heterophilic interactions and bridge the synaptic cleft to induce presynaptic terminals
- Here, we demonstrate that site-specific N-glycosylation impacts the structure and function of adhesive SynCAM interactions
- Through crystallographic analysis of SynCAM 2 , we identified within the adhesive interface of its Ig1 domain an N-glycan on residue Asn(60)
- Structural modeling of the corresponding SynCAM 1 Ig1 domain indicates that its glycosylation sites Asn(70) /Asn(104) flank the binding interface of this domain
- Mass spectrometric and mutational studies confirm and characterize the modification of these three sites
- These site-specific N-glycans affect SynCAM adhesion yet act in a differential manner
- Although glycosylation of SynCAM 2 at Asn(60) reduces adhesion, N-glycans at Asn(70) /Asn(104) of SynCAM 1 increase its interactions
- The modification of SynCAM 1 with sialic acids contributes to the glycan-dependent strengthening of its binding
- Functionally, N-glycosylation promotes the trans-synaptic interactions of SynCAM 1 and is required for synapse induction
- These results demonstrate that N-glycosylation of SynCAM proteins differentially affects their binding interface and implicate post-translational modification as a mechanism to regulate trans-synaptic adhesion