POSTPONED - Cdk12 maintains the axon initial segment through actin remodelling

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• Dr Gaynor Smith | Cardiff University
• Wednesday 05 October 2022, 15:00-16:00
• MRC MBU, Level 7 Lecture Theatre, The Keith Peters Building, CB2 0XY.

If you have a question about this talk, please contact Hannah Burns.

POSTPONED - new date tbc

In the nervous system the diameter and location of the axon initial segment (AIS) defines neuronal polarity and firing capacity throughout the lifetime of an organism. It is an essential specialized compartment required for action potential initiation and the axon-soma filtration barrier. The actin cytoskeleton is implicated as the key structural component in the AIS , however the mechanisms controlling these functions in vivo remains elusive. We identify Cdk12 as a negative regulator of actin dynamics, AIS size, physiology and neuronal maintenance during ageing. Cdk12 maintains proximal axonal width through the transcription of homeostatic enzymes in the 1-carbon by folate pathway which ultimately utilize the amino acid homocysteine. Loss of Cdk12 leads to elevated homocysteine and in turn increases F-actin formation through cofilin and Arp2/3-dependent mechanisms. Actin remodelling further induces Drp1-dependent fission of axonal mitochondria and the breakdown of filtration barrier, allowing soma restricted organelles to enter the axon. Prolonged loss of Cdk12 in vivo during ageing induces neurodegeneration at sites focal to actin patch formation. Hyperhomocysteinemia, actin changes and mitochondrial fragmentation are associated with several neurodegenerative conditions such as Alzheimer’s disease and we provide a candidate molecular pathway to link together such pathological events.

This talk is part of the MRC Mitochondrial Biology Unit Seminars series.

This talk is included in these lists:

• All Talks (aka the CURE list)
• CamBridgeSens
• Cambridge talks
• Life Science Interface Seminars
• MRC MBU, Level 7 Lecture Theatre, The Keith Peters Building, CB2 0XY
• MRC Mitochondrial Biology Unit Seminars
• Trust & Technology Initiative - interesting events

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