LRRTMs Organize Synapses through Differential Engagement of Neurexin and PTPσ.

Abstract:

: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.

journal_name

Neuron

journal_title

Neuron

authors

Roppongi RT,Dhume SH,Padmanabhan N,Silwal P,Zahra N,Karimi B,Bomkamp C,Patil CS,Champagne-Jorgensen K,Twilley RE,Zhang P,Jackson MF,Siddiqui TJ

doi

10.1016/j.neuron.2020.01.003

subject

Has Abstract

pub_date

2020-04-08 00:00:00

pages

108-125.e12

issue

1

eissn

0896-6273

issn

1097-4199

pii

S0896-6273(20)30003-9

journal_volume

106

pub_type

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