Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/79343
Title: Cell biological mechanisms of activity-dependent synapse to nucleus translocation of CRTC1 in neurons
Authors: Toh, Hean Ch'ng
DeSalvo, Martina
Lin, Peter
Vashisht, Ajay
Wohlschlegel, James A.
Martin, Kelsey C.
Issue Date: 2015
Source: Toh, H. C., DeSalvo, M., Lin, P., Vashisht, A., Wohlschlegel, J. A., & Martin, K. C. (2015). Cell biological mechanisms of activity-dependent synapse to nucleus translocation of CRTC1 in neurons. Frontiers in Molecular Neuroscience, 8, 48-.
Series/Report no.: Frontiers in Molecular Neuroscience
Abstract: Previous studies have revealed a critical role for CREB-regulated transcriptional coactivator (CRTC1) in regulating neuronal gene expression during learning and memory. CRTC1 localizes to synapses but undergoes activity-dependent nuclear translocation to regulate the transcription of CREB target genes. Here we investigate the long-distance retrograde transport of CRTC1 in hippocampal neurons. We show that local elevations in calcium, triggered by activation of glutamate receptors and L-type voltage-gated calcium channels, initiate active, dynein-mediated retrograde transport of CRTC1 along microtubules. We identify a nuclear localization signal within CRTC1, and characterize three conserved serine residues whose dephosphorylation is required for nuclear import. Domain analysis reveals that the amino-terminal third of CRTC1 contains all of the signals required for regulated nucleocytoplasmic trafficking. We fuse this region to Dendra2 to generate a reporter construct and perform live-cell imaging coupled with local uncaging of glutamate and photoconversion to characterize the dynamics of stimulus-induced retrograde transport and nuclear accumulation.
URI: https://hdl.handle.net/10356/79343
http://hdl.handle.net/10220/38742
ISSN: 1662-5099
DOI: 10.3389/fnmol.2015.00048
Rights: Copyright © 2015 Ch’ng, DeSalvo, Lin, Vashisht, Wohlschlegel and Martin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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