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Combinatorial expression of neurexins and LAR-type phosphotyrosine phosphatase receptors instructs assembly of a cerebellar circuit

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  • Alessandra Sclip

    (Stanford University School of Medicine)

  • Thomas C. Südhof

    (Stanford University School of Medicine
    Stanford University School of Medicine)

Abstract

Synaptic adhesion molecules (SAMs) shape the structural and functional properties of synapses and thereby control the information processing power of neural circuits. SAMs are broadly expressed in the brain, suggesting that they may instruct synapse formation and specification via a combinatorial logic. Here, we generate sextuple conditional knockout mice targeting all members of the two major families of presynaptic SAMs, Neurexins and leukocyte common antigen-related-type receptor phospho-tyrosine phosphatases (LAR-PTPRs), which together account for the majority of known trans-synaptic complexes. Using synapses formed by cerebellar Purkinje cells onto deep cerebellar nuclei as a model system, we confirm that Neurexins and LAR-PTPRs themselves are not essential for synapse assembly. The combinatorial deletion of both neurexins and LAR-PTPRs, however, decreases Purkinje-cell synapses on deep cerebellar nuclei, the major output pathway of cerebellar circuits. Consistent with this finding, combined but not separate deletions of neurexins and LAR-PTPRs impair motor behaviors. Thus, Neurexins and LAR-PTPRs are together required for the assembly of a functional cerebellar circuit.

Suggested Citation

  • Alessandra Sclip & Thomas C. Südhof, 2023. "Combinatorial expression of neurexins and LAR-type phosphotyrosine phosphatase receptors instructs assembly of a cerebellar circuit," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40526-0
    DOI: 10.1038/s41467-023-40526-0
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    References listed on IDEAS

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    1. Markus Missler & Weiqi Zhang & Astrid Rohlmann & Gunnar Kattenstroth & Robert E. Hammer & Kurt Gottmann & Thomas C. Südhof, 2003. "α-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis," Nature, Nature, vol. 423(6943), pages 939-948, June.
    2. Ai-Hui Tang & Haiwen Chen & Tuo P. Li & Sarah R. Metzbower & Harold D. MacGillavry & Thomas A. Blanpied, 2016. "A trans-synaptic nanocolumn aligns neurotransmitter release to receptors," Nature, Nature, vol. 536(7615), pages 210-214, August.
    3. Xuchen Zhang & Pei-Yi Lin & Kif Liakath-Ali & Thomas C. Südhof, 2022. "Teneurins assemble into presynaptic nanoclusters that promote synapse formation via postsynaptic non-teneurin ligands," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    4. Tomoyuki Yoshida & Atsushi Yamagata & Ayako Imai & Juhyon Kim & Hironori Izumi & Shogo Nakashima & Tomoko Shiroshima & Asami Maeda & Shiho Iwasawa-Okamoto & Kenji Azechi & Fumina Osaka & Takashi Saito, 2021. "Canonical versus non-canonical transsynaptic signaling of neuroligin 3 tunes development of sociality in mice," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
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