Speaker

Philip Freund, Department of Biomolecular Sciences, Weizmann Institute of Science, Israel

Title

Role of axonal importin β1 in presynaptic local translation and spatial memory

Abstract

Intracellular transport is essential for neuronal health and function, and enables fast communication of distal signals. The importin family of nucleocytoplasmic transport factors also has key roles in transport along neuronal processes. In previous studies, we generated an importin β1 3’UTR deletion (3’UTR^KO) mouse line, and demonstrated that this causes subcellular reduction of importin β1 mRNA and protein in axons. Here I report that importin β1 3’UTR^KO mice exhibit a significant and consistent spatial memory deficit, with electrophysiological analysis of hippocampal circuits showing a specific impairment in presynapse-dependent mossy fiber long-term potentiation. Mass-spectrometry revealed an altered synaptic proteome, and RNA sequencing showed a significant down-regulation of locally translated presynaptic mRNAs in importin β1 3’UTR^KO neurons. This dysregulation is reflected in a reduced synaptic vesicle readily-releasable pool. These findings suggest that importin β1 takes part in shaping local presynaptic translatome, proteome, and phosphatome landscapes, ultimately reflected in a physiologically-relevant behavioral phenotype.

Biography

I am currently a 5^th-year PhD student in the laboratory of Mike Fainzilber, at the Weizmann Institute of Science (Rehovot, Israel). I completed my undergraduate studies in 2019, at Lake Forest College, IL, USA, focusing on molecular neuroscience and cell biology. During my MSc at Weizmann I primarily studied the anxiolytic effects of β-sitosterol in mice, and the paper regarding this project was published in 2021. Currently I am investigating the involvement of importin β1 in synaptic plasticity and memory, and the role of importin α isoforms in transcription factor nuclear import, among other side-projects. My scientific philosophy is oriented towards integrating molecular and behavioral neuroscience approaches; studying problems both bottom-up from the protein-protein interaction level, and top-down by investigating intriguing behavioral phenotypes.