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SUMMARY:POSTPONED - Cdk12 maintains the axon initial segment through actin
  remodelling - Dr Gaynor Smith | Cardiff University
DTSTART:20221005T140000Z
DTEND:20221005T150000Z
UID:TALK165364@talks.cam.ac.uk
CONTACT:Hannah Burns
DESCRIPTION:In the nervous system the diameter and location of the axon in
 itial segment (AIS) defines neuronal polarity and firing capacity througho
 ut the lifetime of an organism. It is an essential specialized compartment
  required for action potential initiation and the axon-soma filtration bar
 rier. The actin cytoskeleton is implicated as the key structural component
  in the AIS\, however the mechanisms controlling these functions in vivo r
 emains elusive. We identify Cdk12 as a negative regulator of actin dynamic
 s\, AIS size\, physiology and neuronal maintenance during ageing. Cdk12 ma
 intains proximal axonal width through the transcription of homeostatic enz
 ymes in the 1-carbon by folate pathway which ultimately utilize the amino 
 acid homocysteine. Loss of Cdk12 leads to elevated homocysteine and in tur
 n increases F-actin formation through cofilin and Arp2/3-dependent mechani
 sms. Actin remodelling further induces Drp1-dependent fission of axonal mi
 tochondria and the breakdown of filtration barrier\, allowing soma restric
 ted organelles to enter the axon. Prolonged loss of Cdk12 in vivo during a
 geing induces neurodegeneration at sites focal to actin patch formation. H
 yperhomocysteinemia\, actin changes and mitochondrial fragmentation are as
 sociated with several neurodegenerative conditions such as Alzheimer’s d
 isease and we provide a candidate molecular pathway to link together such 
 pathological events. 
LOCATION:MRC MBU\, Level 7 Lecture Theatre\, The Keith Peters Building\, C
 B2 0XY
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