Proline-rich synapse-associated protein-1 and 2 (ProSAP1/Shank2 and ProSAP2/Shank3)-scaffolding proteins are also present in postsynaptic specializations of the peripheral nervous system.

Proline-rich synapse-associated protein-1 and 2 (ProSAP1/Shank2 and ProSAP2/Shank3) were originally found as synapse-associated protein 90/postsynaptic density protein-95-associated protein (SAPAP)/guanylate-kinase-associated protein (GKAP) interaction partners and also isolated from synaptic junctional protein preparations of rat brain. They are essential components of the postsynaptic density (PSD) and are specifically targeted to excitatory asymmetric type 1 synapses. Functionally, the members of the ProSAP/Shank family are one of the postsynaptic key elements since they link and attach the postsynaptic signaling apparatus, for example N-methyl-d-aspartic acid (NMDA)-receptors via direct and indirect protein interactions to the actin-based cytoskeleton. The functional significance of ProSAP1/2 for synaptic transmission and the paucity of data with respect to the molecular composition of PSDs of the peripheral nervous system (PNS) stimulated us to investigate neuromuscular junctions (NMJs), synapses of the superior cervical ganglion (SCG), and synapses in myenteric ganglia as representative synaptic junctions of the PNS. Confocal imaging revealed ProSAP1/2-immunoreactivity (-iry) in NMJs of rat and mouse sternomastoid and tibialis anterior muscles. In contrast, ProSAP1/2-iry was only negligibly found in motor endplates of striated esophageal muscle probably caused by antigen masking or a different postsynaptic molecular anatomy at these synapses. ProSAP1/2-iry was furthermore detected in cell bodies and dendrites of superior cervical ganglion neurons and myenteric neurons in esophagus and stomach. Ultrastructural analysis of ProSAP1/2 expression in myenteric ganglia demonstrated that ProSAP1 and ProSAP2 antibodies specifically labelled PSDs of myenteric neurons. Thus, scaffolding proteins ProSAP1/2 were found within the postsynaptic specializations of synapses within the PNS, indicating a similar molecular assembly of central and peripheral postsynapses.