LKCMedicine Lecture Series by Asst Prof Chng Toh Hean

Transcription

LKCMedicine Lecture Series by Asst Prof Chng Toh Hean
LKCMedicine Lecture Series
Synapse to Nucleus Signalling in Neurons:
How Long Distance Transport of Proteins Can
Regulate the Encoding of Long Term Memories
Asst Prof Ch’ng Toh Hean, Nanyang Assistant Professor at
Lee Kong Chian School of Medicine and School of Biological
Sciences, NTU
Chaired by Prof Balázs Gulyás, Lee Kong Chian School of
Medicine, NTU
Date:
Time:
Venue:
29 April 2015, Wednesday
5.30pm – 6.30pm
LKCMedicine Novena Campus
Level 2, Seminar Room
11 Mandalay Road, Singapore 308232
Synopsis
Long-lasting changes in synaptic efficacy associated with the encoding of long term memories require
transcription of new genes and synthesis of new proteins. The transport of synaptically-localised
transcriptional regulators during neuronal activity provides a method of coupling synaptic activation
with changes in the transcription. Asst Prof Chng’s lab is interested in studying the molecular basis of
long term memory formation as a means to identify better targets and develop more effective therapies
for various neurological and neurodegenerative disorders. Using a multidisciplinary approach, they
seek to characterise the types of signals generated at the synapse, how they are transported to the
nucleus and finally, which genes are being regulated during transcription-dependent plasticity.
Recently, the lab has characterised a potent transcriptional coactivator known as CRTC1 which
binds and activates the transcription factor CREB. They showed that CRTC1 undergoes long
distance, activity-dependent transport from the synapse to the nucleus to promote
CRE-driven transcription during synaptic stimulation associated with hippocampal plasticity.
The lab also demonstrates that nuclear translocation of CRTC1 is highly regulated
by its phosphorylation state while the nuclear persistence is modulated by cAMP. The results
indicate that nuclear translocation of synaptic proteins such as CRTC1 can dynamically
inform the nucleus about changes in synaptic activity.