Details

Autor(en) / Beteiligte

• Roppongi, Reiko T.
• Dhume, Shreya H.
• Padmanabhan, Nirmala
• Silwal, Prabhisha
• Zahra, Nazmeena
• Karimi, Benyamin
• Bomkamp, Claire
• Patil, Chetan S.
• Champagne-Jorgensen, Kevin
• Twilley, Rebecca E.
• Zhang, Peng
• Jackson, Michael F.
• Siddiqui, Tabrez J.

Titel

LRRTMs Organize Synapses through Differential Engagement of Neurexin and PTPσ

Ist Teil von

• Neuron (Cambridge, Mass.), 2020-04, Vol.106 (1), p.108-125.e12

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• Presynaptic neurexins (Nrxs) and type IIa receptor-type protein tyrosine phosphatases (RPTPs) organize synapses through a network of postsynaptic ligands. We show that leucine-rich-repeat transmembrane neuronal proteins (LRRTMs) differentially engage the protein domains of Nrx but require its heparan sulfate (HS) modification to induce presynaptic differentiation. Binding to the HS of Nrx is sufficient for LRRTM3 and LRRTM4 to induce synaptogenesis. We identify mammalian Nrx1γ as a potent synapse organizer and reveal LRRTM4 as its postsynaptic ligand. Mice expressing a mutant form of LRRTM4 that cannot bind to HS show structural and functional deficits at dentate gyrus excitatory synapses. Through the HS of Nrx, LRRTMs also recruit PTPσ to induce presynaptic differentiation but function to varying degrees in its absence. PTPσ forms a robust complex with Nrx, revealing an unexpected interaction between the two presynaptic hubs. These findings underscore the complex interplay of synapse organizers in specifying the molecular logic of a neural circuit. [Display omitted] •LRRTMs require HS but engage different protein domains of Nrx for synaptogenesis•Nrx1γ is a novel presynaptic organizer•The presynaptic hubs, Nrx and PTPσ, cooperate in LRRTM-mediated synaptogenesis•Mice with disrupted LRRTM4-HS interaction have excitatory synaptic deficits Roppongi et al. show that LRRTMs organize synapses through the heparan sulfate modification of neurexins but have a differential requirement for its protein domains. Neurexin cooperates with PTPσ to mediate synaptogenesis by the LRRTMs.