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 for the control of synapse assembly. Their synaptic nanoscale localization, however, has not been established, and the fine structure of synapses after knockout of the three vertebrate genes for LAR-RPTPs (PTPδ, PTPσ and LAR) has not been tested. Here, we find that PTPδ is precisely apposed to postsynaptic scaffolds at excitatory and inhibitory synapses using superresolution microscopy. We generated triple-conditional knockout mice for PTPδ, PTPσ and LAR to test whether they are essential for synapse structure. 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. We conclude that LAR-RPTPs, despite their localization at synaptic appositions, are dispensable for the organization and function of presynaptic nerve terminals.