The beta-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice

Ong-Palsson, Emma; Njavro, Jasenka Rudan; Wilson, Yvette; Pigoni, Martina; Schmidt, Andree; Mueller, Stephan A.; Meyer, Michael; Hartmann, Jana; Busche, Marc Aurel; Gunnersen, Jenny M.; Munro, Kathryn M. und Lichtenthaler, Stefan F. (2021): The beta-Secretase Substrate Seizure 6-Like Protein (SEZ6L) Controls Motor Functions in Mice. In: Molecular Neurobiology, Bd. 59, Nr. 2: S. 1183-1198

Abstract

The membrane protein seizure 6-like (SEZ6L) is a neuronal substrate of the Alzheimer's disease protease BACE1, and little is known about its physiological function in the nervous system. Here, we show that SEZ6L constitutive knockout mice display motor phenotypes in adulthood, including changes in gait and decreased motor coordination. Additionally, SEZ6L knockout mice displayed increased anxiety-like behaviour, although spatial learning and memory in the Morris water maze were normal. Analysis of the gross anatomy and proteome of the adult SEZ6L knockout cerebellum did not reveal any major differences compared to wild type, indicating that lack of SEZ6L in other regions of the nervous system may contribute to the phenotypes observed. In summary, our study establishes physiological functions for SEZ6L in regulating motor coordination and curbing anxiety-related behaviour, indicating that aberrant SEZ6L function in the human nervous system may contribute to movement disorders and neuropsychiatric diseases.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin ; Medizin > Munich Cluster for Systems Neurology (SyNergy)
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 0893-7648
• Sprache: Englisch
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198