RAB35 is required for murine hippocampal development and functions by regulating neuronal cell distribution

Author:

Maejima IkukoORCID,Hara Taichi,Tsukamoto SatoshiORCID,Koizumi Hiroyuki,Kawauchi TakeshiORCID,Akuzawa Tomoko,Hirai Rika,Kobayashi Hisae,Isobe Inoya,Emoto KazuoORCID,Kosako HidetakaORCID,Sato KenORCID

Abstract

AbstractRAB35 is a multifunctional small GTPase that regulates endocytic recycling, cytoskeletal rearrangement, and cytokinesis. However, its physiological functions in mammalian development remain unclear. Here, we generatedRab35-knockout mice and found that RAB35 is essential for early embryogenesis. Interestingly, brain-specificRab35-knockout mice displayed severe defects in hippocampal lamination owing to impaired distribution of pyramidal neurons, although defects in cerebral cortex formation were not evident. In addition,Rab35-knockout mice exhibited defects in spatial memory and anxiety-related behaviors. Quantitative proteomics indicated that the loss of RAB35 significantly affected the levels of other RAB proteins associated with endocytic trafficking, as well as some neural cell adhesion molecules, such as contactin-2. Collectively, our findings revealed that RAB35 is required for precise neuronal distribution in the developing hippocampus by regulating the expression of cell adhesion molecules, thereby influencing spatial memory.

Funder

Takeda Science Foundation

MEXT | Japan Society for the Promotion of Science

Publisher

Springer Science and Business Media LLC

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

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