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The role of the ezrin-radixin-moesin (ERM) proteins in development and post-injury responses of central nervous system neurons

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Haas, Matilda Ann (2006) The role of the ezrin-radixin-moesin (ERM) proteins in development and post-injury responses of central nervous system neurons. PhD thesis, University of Tasmania.

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Abstract

The ezrin-radbdn-moesin (ERM) family of proteins mediate diverse cytoskeletal
processes, such as cell adhesion and morphology, as well as cell migration. These
functions have primarily been elucidated in non-neuronal cell phenotypes, with only
limited data pertaining to a role for ERM proteins in CNS neurons. The few studies
examining ERM functions in neurons indicate that they contribute to important aspects
of developmental neuron growth and morphogenesis; processes that must be precisely
executed for the establishment of appropriate connectivity during brain development.
Further alluding to their potential importance in the CNS was the identification of ezrin
as a binding partner of the developmentally crucial cell adhesion molecule (CAM) L1.
After completion of brain development, the mature CNS has very little capacity for
regeneration and functional recovery following injury, partly because upon maturation
neurons lose their intrinsic ability for substantial growth, but mainly because the mature
nervous system environment is inhibitory to growth, particularly following traumatic
injury. Therefore, a current and widely accepted theory is that recapitulation of aspects
of CNS development is required for regeneration to occur in the more mature nervous
system. Thus, investigation of developmentally significant proteins may provide clues
as to the requirements for more mature CNS neurons to mount a regenerative response.
This thesis investigated ERM protein function in CNS neurons, both during
development and regeneration, with investigations focussed on ERM proteins' binding
relationship with L1. ERM proteins were specifically expressed during early neuronal
morphogenesis, localised to areas associated with motility and growth, and they co-localised
with L1, particularly in the axonal growth cone. Perturbation of ERM proteins
function utilising transfection of a dominant negative form of ezrin implicated ERMs in
multiple aspects of development, including neurite initiation and outgrowth, growth
cone morphology, neurite branching and neuron migration. Investigation of ERM
function in models of injury to mature neurons demonstrated a re-expression of ERM
proteins, potentially to participate in regenerative attempts, including neurite initiation and outgrowth, as well as post-injury neuron motility. Interrupting ERM activation
using an inhibitor of Rho kinase significantly perturbed many of these developmental
and post-injury functions, confirming a role for Rho kinase in ERM activation. These
results show that ERM proteins play significant roles in aspects of neuronal growth and
morphology in both developing and regenerating CNS neurons. Furthermore,
elucidation of the roles of ERM proteins and L1 show that common mechanisms are
required for developmental and regenerative nervous system growth, which is important
for uncovering potential mechanisms of regenerative growth, and identifying therapeutic
targets for encouraging post-injury regeneration.

Item Type: Thesis (PhD)
Keywords: Central nervous system, Neurons, Brain
Copyright Holders: The Author
Additional Information:

Available for library use only and copying in accordance with the Copyright Act 1968, as amended. Thesis (PhD)--University of Tasmania, 2006. Includes bibliographical references. Ch. 1. Introduction -- Ch. 2. Materials and methods -- Ch. 3. Localisation and perturbation of ERM proteins in developing CNS neurons -- Ch. 4. The role of ERM proteins and L1 in developmental and post-injury regenerative neurite outgrowth -- Ch. 5. Identification and characterisation of a population of motile neurons which express ERM proteins, in long-term cortical culture -- Ch. 6. Rho kinase activates ERM proteins and mediates their function in cortial neuron growth, morphology and motility -- Ch. 7. Discussion

Date Deposited: 09 Dec 2014 00:11
Last Modified: 11 Mar 2016 05:54
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