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LAR-RPTPs Directly Interact with Neurexins to Coordinate Bidirectional Assembly of Molecular Machineries

Title
LAR-RPTPs Directly Interact with Neurexins to Coordinate Bidirectional Assembly of Molecular Machineries
Author(s)
Han, Kyung AhKim, YJYoon, Taek HanKim, HyeonhoBae, SungwonUm, Ji WonChoi, SYKo, Jaewon
DGIST Authors
Han, Kyung AhKim, YJYoon, Taek HanKim, HyeonhoBae, SungwonUm, Ji WonChoi, SYKo, Jaewon
Issued Date
2020-10
Type
Article
Author Keywords
alternative splicingheparan sulfatesLAR-RPTPsneurexinsynaptic adhesionsynaptogenic
Keywords
SYNAPTIC ADHESION MOLECULESPTP-SIGMALIPRIN-ALPHARECEPTORNEUROLIGINSPROTEINSDIFFERENTIATIONHIPPOCAMPALCOMPLEXESSYNAPSES
ISSN
0270-6474
Abstract
Neurexins (Nrxns) and LAR-RPTPs (leukocyte common antigen-related protein tyrosine phosphatases) are presynaptic adhesion proteins responsible for organizing presynaptic machineries through interactions with nonoverlapping extracellular ligands. Here, we report that two members of the LAR-RPTP family, PTPr and PTPd, are required for the presynaptogenic activity of Nrxns. Intriguingly, Nrxn1 and PTPr require distinct sets of intracellular proteins for the assembly of specific presynaptic terminals. In addition, Nrxn1a showed robust heparan sulfate (HS)-dependent, high-affinity interactions with Ig domains of PTPr that were regulated by the splicing status of PTPr. Furthermore, Nrxn1a WT, but not a Nrxn1a mutant lacking HS moieties (Nrxn1a DHS), inhibited postsynapse-inducing activity of PTPr at excitatory, but not inhibitory, synapses. Similarly, cis expression of Nrxn1a WT, but not Nrxn1a DHS, suppressed the PTPr-mediated maintenance of excitatory postsynaptic specializations in mouse cultured hippocampal neurons. Lastly, genetics analyses using male or female Drosophila Dlar and Dnrx mutant larvae identified epistatic interactions that control synapse formation and synaptic transmission at neuromuscular junctions. Our results suggest a novel synaptogenesis model whereby different presynaptic adhesion molecules combine with distinct regulatory codes to orchestrate specific synaptic adhesion pathways. © 2020 the authors
URI
http://hdl.handle.net/20.500.11750/13156
DOI
10.1523/JNEUROSCI.1091-20.2020
Publisher
Society for Neuroscience
Related Researcher
  • 엄지원 Um, Ji Won 뇌과학과
  • Research Interests Molecular and cellular mechanisms underlying synapse elimination; Key synaptic mechanisms associated with Alzheimer's disease and autism spectrum disorders; Synaptic homeostasis
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Appears in Collections:
Department of Brain Sciences Laboratory of Synapse Formation and Function 1. Journal Articles
Department of Brain Sciences Synapse Disorder Laboratory 1. Journal Articles

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