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Title: Exploring novel aspects of PICK1 function
Author: Antoniou, Anna
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2013
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The molecular mechanisms that mediate long-term changes at neuronal synapses involve functional and structural rearrangements at dendritic spines and underlie the molecular basis for information storage in the brain. The BAR- and PDZ-containing protein PICK1 (protein interacting with C-kinase) has a well-established role in the activity-dependent trafficking of AMPA receptors in NMDAR-induced long-term depression (LTD), and regulates spine morphology by inhibiting the Arp2/3 complex. Recently published work by members of the Hanley lab and collaborators demonstrates that the small GTPase Arfi is a major regulator of PICK1 function in LTD. I contributed to this work by investigating the functional role of Arf1 on actin dynamics using fluorescence recovery after photobleaching (FRAP), where endogenous F-actin turnover was quantified using constructs expressing lifeact-GFP. Knockdown of Arf1 slowed F-actin dynamics, which was rescued by wild type Arf1, but not the PICK1-binding mutant. Importantly, these effects were absent in spines with reduced levels of PICKi, which indicates that PICK1 is a novel Arf1 effector by modulating Arp2/3-mediated regulation of the actin cytoskeleton in spines.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available