Cofilin Research Paper

Role of DISC1 and its interactions with Cofilin in pathways leading to Synaptic Plasticity

Abstract
Cofilin is an actin depolymerization factor responsible for severance of actin filaments in dendritic spines. Cofilin is activated upon de-phosphorylation via slingshot phosphatase (SSH) and deactivated when phosphorylated by LIM-kinase (LIMK). Phosphorylation of Cofilin results in polymerization of F-actin therefore formation of dendritic spines which is associated with
LTP. Peptide drugs S3 and p-S3 are known to decrease and increase expression of phosphorylated-cofilin by inhibiting LIMK and SHH, respectively. In our studies we have isolated and treated hippocampal slices of C57 wildtype mice with S3 and p-S3 drugs and
observed
Cofilin is activated upon dephosphorylation allowing it to bind to the actin cytoskeleton hence enabling its depolymerization activities leading to actin assembly and remodeling of the cytoskeleton [1315]. Two proteins are involved in the regulation of Cofilin; LIM-kinase (LIMK) acts to phosphorylate and deactivate Cofilin resulting in polymerization and stabilization of actin
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filaments thus suppression of actin turnover whereas Slingshot phosphatase (SSH) acts to dephosphorylate and activate Cofilin resulting in severance and depolymerization of actin filaments hence promotion of actin turnover [4, 7, 16, 17]. In the light of previous studies we know that peptide drug p-S3 prevents Cofilin dephosphorylation (activation) by inhibiting SHH whereas S3 prevents Cofilin phosphorylation (deactivation) by blocking LIMK [18, 19].
The purpose of this study is to determine the efficacy of the drugs S3 and p-S3 on hippocampal brain slices of C57 wildtype (WT) mice. Upon treatment of hippocampal slices of C57 WT mice with S3 and p-S3 drugs, we expect to see decreased and increased expression of
It is likely that more change in p-Cofilin expression could have been observed with increased treatment duration of both drugs.
Intracellular mechanisms involved in regulation of spine morphology contributes to our understanding of persistent changes in synaptic connections that lead to long term potentiation and long term depression. Cofilin is a key converging point of several pathways that lead to either formation or shrinkage of dendritic spines. Delineation of promoters and inhibitors responsible in mediating Cofilin activation is therefore important as they can provide us with novel therapeutic agents against neurological disorders such as depression and/or schizophrenia.

Acknowledgements
Instructions on how to perform all experimental protocols were given by Ner Mu Nar Saw, PHD student at Jia Lab, Department of Neuroscience and Mental Health, Hospital for Sick Children.

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Extraction of hippocampal slices using a vibratome as well as Western blot and data analysis were done by me.
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