Professor Ken Sato and Assistant Professor Ikuko Maejima in the Laboratory of Molecular Traffic, in collaboration with Waseda University, National Institutes for Quantum and Radiological Science and Technology, the University of Tokyo, Kyoto University, Ohu University, and Tokushima University, has revealed that RAB35 is required for hippocampal development and functions by regulating neuronal cell distribution. RAB35 is known to be a multifunctional small GTPase that regulates endocytic recycling, cytoskeletal rearrangement, and cytokinesis. We found that brain-specific Rab35-knockout mice exhibit severe defects in hippocampal lamination due to impaired distribution of pyramidal neurons. We also revealed that Rab35-knockout mice show defects in spatial memory and anxiety-related behaviors. 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. Our study are expected to contribute to the elucidation of the pathophysiology of neurodegenerative diseases by elucidating one aspect of the regulation of higher brain functions regulated by the intracellular membrane trafficking system.

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