Heparan Sulfate Organizes Neuronal Synapses through Neurexin Partnerships.
Cell
; 174(6): 1450-1464.e23, 2018 09 06.
Article
em En
| MEDLINE
| ID: mdl-30100184
ABSTRACT
Synapses are fundamental units of communication in the brain. The prototypical synapse-organizing complex neurexin-neuroligin mediates synapse development and function and is central to a shared genetic risk pathway in autism and schizophrenia. Neurexin's role in synapse development is thought to be mediated purely by its protein domains, but we reveal a requirement for a rare glycan modification. Mice lacking heparan sulfate (HS) on neurexin-1 show reduced survival, as well as structural and functional deficits at central synapses. HS directly binds postsynaptic partners neuroligins and LRRTMs, revealing a dual binding mode involving intrinsic glycan and protein domains for canonical synapse-organizing complexes. Neurexin HS chains also bind novel ligands, potentially expanding the neurexin interactome to hundreds of HS-binding proteins. Because HS structure is heterogeneous, our findings indicate an additional dimension to neurexin diversity, provide a molecular basis for fine-tuning synaptic function, and open therapeutic directions targeting glycan-binding motifs critical for brain development.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Sinapses
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Moléculas de Adesão de Célula Nervosa
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Heparitina Sulfato
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2018
Tipo de documento:
Article