Award details

CAMSAP1: relationship of structure to function in the process of neurite outgrowth

Reference	BB/D017823/1
Principal Investigator / Supervisor	Dr Anthony Baines
Co-Investigators / Co-Supervisors
Institution	University of Kent
Department	Sch of Biosciences
Funding type	Research
Value (£)	302,728
Status	Completed
Type	Research Grant
Start date	01/05/2006
End date	30/04/2009
Duration	36 months

Abstract

The formation of nervous systems requires the growth from the bodies of nerve cells of long neurites (axons and dendrites) that connect with target cells. In work funded by BBSRC, we have discovered a novel protein required for neurite outgrowth from the model cell line PC12. This protein, CAMSAP1, is a calmodulin-regulated spectrin-associated protein. In this project, we aim to define aspects of the mechanism that links CAMSAP1 to the process of neurite outgrowth. In particular, we will investigate the relationship between spectrin and calmodulin binding to CAMSAP1 and the process of neurite outgrowth. The main cell model for these studies will be rat PC12 cells, but we will cross-compare results using this cell line with primary neural cultures from rats. Specifically, we aim to: 1. Define the domains of CAMSAP1 that are essential for neurite outgrowth 2. Define amino acid residues in CAMSAP1 that are essential for binding to spectrin and calmodulin by mutagenesis. 3. Compare the activities of wild-type and CAMSAP1 mutants that do not bind spectrin or calmodulin in neurite outgrowth. 4. Define further the interactions of CAMSAP1 by pull-down assays and immunoprecipitation. The outcome of this project will be novel insight into the mechanisms that link CAMSAP1, spectrin and calmodulin regulation to neurite outgrowth.

Summary

To form a functioning nervous system, nerve cells must make connections with other cells so as to send and receive signals. They do this by extending long 'neurites' that grow away from the cell body until they find their target cell and adhere to it. The processes by which neurites grow are therefore absolutely fundamental to the formation and function of nervous systems. In our recent work funded by BBSRC, we have discovered a previously unknown protein that is an essential part of the process of neurite outgrowth. We have identified the gene that encodes this protein, and have found that blocking the expression of this gene stops the extension of neurites. In this project, we aim to learn more of the mechanism(s) that link this protein to neurite outgrowth. In particular, we wish to discover how the protein works together with other components of the process. The outcome of this project will be new insight into the mechanisms that underlie all function in nervous systems.

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	Neuroscience and Behaviour
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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