Study of the involvement of collybistin and gephyrin proteins in the control of translation initiation

Abstract

Collybistin and gephyrin are key proteins implicated in inhibitory synapse development and plasticity that cluster and localize inhibitory neurotransmitter receptors to the neural postsynaptic membrane. Loss of function mutations of collybistin and gephyrin have been identified in patients with neurological diseases such as mental retardation, epilepsy and autism. We have recently reported that collybistin and gephyrin interact with a protein complex that controls translation initiation in eukaryotic cells (eIF3 complex), suggesting that these proteins may also act as regulators of protein synthesis in human cells. However, this novel collybistin and gephyrin function must be confirmed in further studies. Therefore, the major objective of this research project is to verify if collybistin and gephyrin are indeed involved in the control of translation initiation. More specific goals for the project are to verify whether collybistin and gephyrin: a) interact with other proteins involved in translation initiation control; b) are involved in the translation initiation complex formation; c) participate in mTOR signaling pathway; d) are involved in the control of translation in humans cells. By reaching these objectives, this project intends to get a better understanding of collybistin and gephyrin functions, as well as the molecular mechanisms involved in translation initiation. In addition, this knowledge may contribute to unravel possible mechanisms underlying mental retardation and autism, which may allow the development of new and more effective treatments for these patients.