| Abstract |
The work presented in the following pages focuses on the elucidation of the molecular mechanisms underlying neuronal plasticity, in terms of learning and memory, in the nematode
Caenorhabditis elegans. Neuronal plasticity appears to be conserved among different species and can be observed through changes in the animal’s behavior after certain experiences. The nervous system processes and integrates sensory input to generate both immediate responses
and long-term changes in behavior. The nematode worm Caenorhabditis elegans displays a remarkable capacity for experience-induced changes in behavior and several such paradigms
have been described so far. Modulation of behavior by past experience is a manifestation of the C. elegans learning and memory capacity.
Here, we report the identification of PQN-21, a C. elegans protein bearing a Q/N richprion domain, as modulator of learning and memory processes. Prions are infectious agents implicated in a variety of neurodegenerative diseases in mammals, generally referred to as
transmissible spongiform encephalopathies. The glutamine/asparagine (Q/N)-rich domain of prions appears to be responsible for their unusual capacity to fold into structurally and functionally distinct conformations, one of which is self-perpetuating. Usually the selfperpetuating- prion form is organized in self-seeding polymers and can induce other proteins with similar sequences to acquire the prion state, creating a chain reaction. Prion-like proteins are widespread (found in mammals, fungi, yeast), conserved and serve diverse functions. In the
sea snail Aplysia californica, the prion-like neuronal protein CPEB (Si et al., 2003) functions as a positive regulator of mRNA translation in stimulated synapses and helps to maintain longterm synaptic changes associated with memory acquisition and storage.
We find that pqn-21 is expressed in C. elegans neuronal and glial cells and that PQN-21 localizes in the nucleus. Deletion of the pqn-21 gene results in defective gonadal outgrowth and
egg-laying. Interestingly, while PQN-21-depleted animals display normal chemotaxis to several soluble and volatile compounds, they show strongly impaired conditioning to chemicals,
indicating a shortfall in associative learning and memory, as well as impaired olfactory adaptation. In addition, we find that mutants with defective glial cells show a similar phenotype.
Relative to this, we showed that expression of PQN-21 in glial cells is necessary for olfactory adaptation. Based on these observations, we conclude that prion-like PQN-21 protein functions in glial cells to facilitate learning and memory. Given the conserved function of prion-like
proteins among diverse species, C. elegans offers an attractive and versatile platform in which
to dissect the relevant mechanisms. To this end, we are characterizing the function of PQN-21, the neuronal circuit that mediates these behaviors and the involvement of glial cells in certain
paradigms of learning and memory in C. elegans.
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Γλοιακά κύτταρα και μηχανισμοί μνήμης και μάθησης στο Caenorhabditis elegants : ο ρόλος της πρωτείνης PQN-21
