Saitoh Yurika, Motofuji Sayaka, Kamijo Akio, Suzuki Tatsuo, Yoshizawa Takahiro, Sakamoto Takeharu, Kametani Kiyokazu, Terada Nobuo
Center for Medical Education, Teikyo University of Science, 2-2-1 Senjusakuragi, Adachi-Ku, Tokyo, 120-0045, Japan.
Division of Biosciences, Teikyo University of Science Graduate School of Science & Engineering, Adachi-ku, Tokyo, Japan.
Histochem Cell Biol. 2025 May 13;163(1):50. doi: 10.1007/s00418-025-02378-1.
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.
膜棕榈酰化蛋白6（MPP6）是一种膜骨架蛋白，不仅在外周神经系统（PNS）中表达，在中枢神经系统（CNS）中也有表达。在本研究中，我们研究了MPP6及其相关蛋白复合物在小鼠大脑中的定位，以及使用MPP6蛋白缺陷（Mpp6-/-）小鼠对其行为的影响。在小鼠脑裂解物和突触膜组分中检测到MPP6，它在其中与其他MPP家族成员形成蛋白复合物，包括MPP1、MPP2和钙/钙调蛋白依赖性丝氨酸蛋白激酶（CASK）。然而，这些复合物的量在Mpp6-/-和野生型（Mpp6+/+）小鼠之间没有差异。免疫组织化学显示，MPP6定位于整个大脑的突触处，特别是在突触后区域。超微结构分析表明，与Mpp6+/+小鼠相比，Mpp6-/-小鼠的突触间隙距离和突触后致密厚度略有减小。在高架十字迷宫试验中，Mpp6-/-小鼠表现出Mpp6+/+小鼠未观察到的异常行为，尽管两组在开放臂和封闭臂中停留的时间没有统计学上的显著差异。运动活动测量显示，与Mpp6+/+小鼠相比，MPP6-/-小鼠在午夜时更活跃，而从早晨到中午则不太活跃，这意味着睡眠-觉醒调节发生了改变。这些发现表明，MPP6通过与其他MPP家族成员和信号蛋白形成蛋白复合物在突触功能中发挥作用。
