Prickle promotes the formation and maintenance of glutamatergic synapses by stabilizing the intercellular planar cell polarity complex.

Ban, Yue; Yu, Ting; Feng, Bo; Lorenz, Charlotte; Wang, Xiaojia; Baker, Clayton; Zou, Yimin · Sci Adv · 2021

basic_science · Level V

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Abstract

Whether there exists a common signaling mechanism that assembles all glutamatergic synapses is unknown. We show here that knocking out <i>Prickle1</i> and <i>Prickle2</i> reduced the formation of the PSD-95–positive glutamatergic synapses in the hippocampus and medial prefrontal cortex in postnatal development by 70–80%. <i>Prickle1</i> and <i>Prickle2</i> double knockout in adulthood lead to the disassembly of 70 to 80% of the postsynaptic-density(PSD)-95–positive glutamatergic synapses. PSD-95–positive glutamatergic synapses in the hippocampus of <i>Prickle2<sup>E8Q/E8Q</sup></i> mice were reduced by 50% at postnatal day 14. Prickle2 promotes synapse formation by antagonizing Vangl2 and stabilizing the intercellular complex of the planar cell polarity (PCP) components, whereas Prickle2 E8Q fails to do so. Coculture experiments show that the asymmetric PCP complexes can determine the presynaptic and postsynaptic polarity. In summary, the PCP components regulate the assembly and maintenance of a large number of glutamatergic synapses and specify the direction of synaptic transmission.