Intact synapse structure and function after combined knockout of PTPδ, PTPσ, and LAR

It has long been proposed that leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) are cell-adhesion proteins that control synapse assembly. Their synaptic nanoscale localization, however, is not established, and synapse fine structure after knockout of the three vertebrate LAR-RPTPs (PTP delta, PTP sigma, and LAR) has not been tested. Here, superresolution microscopy reveals that PTP delta localizes to the synaptic cleft precisely apposed to postsynaptic scaffolds of excitatory and inhibitory synapses. We next assessed synapse structure in newly generated triple-conditional-knockout mice for PTP delta, PTP sigma, and LAR, complementing a recent independent study of synapse function after LAR-RPTP ablation (Sclip and Sud hot 2020). While mild effects on synaptic vesicle clustering and active zone architecture were detected, synapse numbers and their overall structure were unaffected, membrane anchoring of the active zone persisted, and vesicle docking and release were normal. Hence, despite their localization at synaptic appositions, LAR-RPTPs are dispensable for presynapse structure and function.

Automated summary

Despite being localized at synaptic appositions, LAR-RPTPs are shown to be dispensable for presynapse structure and function.