PMID: 20739279

 

    Legend: Gene, Sites

Title : N-glycosylation at the SynCAM ( synaptic cell adhesion molecule ) immunoglobulin interface modulates synaptic adhesion

Abstract :
  1. Select adhesion molecules connect pre- and postsynaptic membranes and organize developing synapses
  2. The regulation of these trans-synaptic interactions is an important neurobiological question
  3. 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
  4. Here, we demonstrate that site-specific N-glycosylation impacts the structure and function of adhesive SynCAM interactions
  5. Through crystallographic analysis of SynCAM 2 , we identified within the adhesive interface of its Ig1 domain an N-glycan on residue Asn(60)
  6. 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
  7. Mass spectrometric and mutational studies confirm and characterize the modification of these three sites
  8. These site-specific N-glycans affect SynCAM adhesion yet act in a differential manner
  9. Although glycosylation of SynCAM 2 at Asn(60) reduces adhesion, N-glycans at Asn(70) /Asn(104) of SynCAM 1 increase its interactions
  10. The modification of SynCAM 1 with sialic acids contributes to the glycan-dependent strengthening of its binding
  11. Functionally, N-glycosylation promotes the trans-synaptic interactions of SynCAM 1 and is required for synapse induction
  12. 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
Output (sent_index, trigger, protein, sugar, site):
  • 0. N-glycosylation, , synaptic cell adhesion molecule, -, -
  • 12. N-glycosylation, , SynCAM proteins, -, -
  • 5. N-glycan, , -, residue, residue Asn(60)
  • 5. residue, , -, -, residue Asn(60)
  • 6. glycosylation, , -, -, sites Asn(70)
  • 6. sites, , -, -, sites Asn(70)
  • 9. glycosylation, , -, -, Asn(60)
  • 9. glycosylation, , SynCAM 2, -, Asn(60)
Output(Part-Of) (sent_index, protein, site):
  • 6. SynCAM 1 Ig1, domain
*Output_Site_Fusion* (sent_index, protein, sugar, site):
  • 5. synaptic cell adhesion molecule, -, residue Asn(60)
  • 5. synaptic cell adhesion molecule, residue, residue Asn(60)
  • 6. synaptic cell adhesion molecule, -, sites Asn(70)
  • 9. SynCAM 2, -, Asn(60)

 

 

Protein NCBI ID SENTENCE INDEX
SynCAM 2 253559 5,9
SynCAM 1 23705 9,10,11
SynCAM 23705 0,4,8
SynCAM 1 Ig1 23705 6
SynCAM proteins 23705 12
synaptic cell adhesion molecules (SynCAMs) 1 and 2 253559 3
synaptic cell adhesion molecule 23705 0