Involvement of membrane palmitoylated protein 6 (MPP6) in synapses of mouse cerebrum

Membrane palmitoylated protein 6 (MPP6), a membrane skeletal protein, is expressed not only in the peripheral nervous system (PNS) but also in the central nervous system (CNS). In this study, we investigated the localization of MPP6 and its associated protein complexes in the mouse cerebrum, as well as its effects on behavior using MPP6 protein-deficient (Mpp6 -/-) mice. MPP6 was detected in mouse cerebral lysates and synaptic membrane fractions, where it formed protein complexes with other MPP family members, including MPP1, MPP2, and calcium/calmodulin-dependent serine protein kinase (CASK). However, the amounts of these complexes did not differ between Mpp6 -/- and wild-type (Mpp6 +/+) mice. Immunohistochemistry revealed that MPP6 was localized at synapses throughout the cerebrum, particularly in the postsynaptic regions. Ultrastructural analysis showed that synaptic cleft distances and postsynaptic density thickness were slightly reduced in Mpp6 -/- mice compared with Mpp6 +/+ mice. In the elevated plus-maze test, a Mpp6 -/- mouse exhibited unusual behavior not observed in Mpp6 +/+ mice, although there was no statistically significant difference in the time spent in the open and closed arms between the two groups. Locomotor activity measurements revealed that MPP6 -/- mice were more active at midnight and less active from morning to noon than Mpp6 +/+ mice, implying alterations in sleep-wake regulation. These findings suggest that MPP6 plays a role in synaptic function by forming protein complexes with other MPP family members and signaling proteins.