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Role of neurexin heparan sulfate in the molecular assembly of synapses - Expanding the neurexin code?
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- Noborn, Fredrik (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
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- Sterky, Fredrik H (author)
- Gothenburg University,Göteborgs universitet,Wallenberg Centre for Molecular and Translational Medicine,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Department of Laboratory Medicine
- (creator_code:org_t)
- 2021-11-09
- 2023
- English.
- In: Febs Journal. - : Wiley. - 1742-464X .- 1742-4658. ; 290:3, s. 252-265
- Journal article (peer-reviewed)
Abstract
Subject headings
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- Synapses are the minimal information processing units of the brain and come in many flavors across distinct circuits. The shape and properties of a synapse depend on its molecular organisation, which is thought to largely depend on interactions between cell adhesion molecules across the synaptic cleft. An established example is that of presynaptic neurexins and their interactions with structurally diverse postsynaptic ligands: the diversity of neurexin isoforms that arise from alternative promoters and alternative splicing specify synaptic properties by dictating ligand preference. The recent finding that a majority of neurexin isoforms exist as proteoglycans with a single heparan sulfate (HS) polysaccharide adds to this complexity. Sequence motifs within the HS polysaccharide may differ between neuronal cell types to contribute specificity to its interactions, thereby expanding the coding capacity of neurexin diversity. However, an expanding number of HS-binding proteins have been found capable to recruit neurexins via the HS chain, challenging the concept of a code provided by neurexin splice isoforms. Here we discuss the possible roles of the neurexin HS in light of what is known from other HS-protein interactions, and propose a model for how the neurexin HS polysaccharide may contribute to synaptic assembly. We also discuss how the neurexin HS may be regulated by co-secreted carbonic anhydrase-related and FAM19A proteins, and highlight some key issues that should be resolved to advance the field.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- CA10
- carbonic anhydrase-related protein
- glycosaminoglycan
- HSPG
- synapse formation
- alpha-neurexins
- binding-sites
- protein
- receptor
- reveals
- domain
- glycosaminoglycans
- proteoglycan
- diversity
- biosynthesis
- Biochemistry & Molecular Biology
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- ref (subject category)
- art (subject category)
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