So far, the protein Tamalin puzzled neuroscientists. Initial evidence suggested that the protein is involved in the regulation of certain receptor functions in nerve cells, but its exact function was unknown. A group of neuroscientists from Ruhr-Universität Bochum and Trinity College in Dublin have now studied the role of Tamalin and discovered that Tamalin is part of the signalling cascade involved in memory formation. The group has published their findings in the journal Frontiers in Synaptic Neuroscience.
Tamalin is a scaffold protein – a substance that combines several proteins into a complex so that they can communicate with each other. This happens through various docking sites – called protein domains – to which other proteins can bind. One of these domains is the PDZ-domain. It allows Tamalin to interact with group 1 metabotropic glutamate receptors located in the cell membrane of neurons.
"Group I metabotropic glutamate receptors are intrinsically involved in hippocampal information storage and synaptic plasticity. Not much is known however about how scaffold proteins regulate the physiological function of these receptors. We explored if Tamalin might help the receptors influence the direction of change of synaptic strength", commented Denise Manahan-Vaughan, the lead scientist of the study.
To study the interaction of Tamalin with the group 1 metabotropic glutamate receptors, mGlu1 and mGlu5, the researchers introduced an artificial peptide into rodent brains to block the interaction of Tamalin with the receptors. The research group then examined the effects of this interruption on synaptic plasticity in the hippocampus of the animals.
Synaptic plasticity describes the ability of nerve cells to reduce or enhance signal transmission at cell junctions, called synapses. It is a key cellular mechanism underlying long-term associative memory. If signal transmission at a synapse is persistently weakened, it is called long-term depression (LTD); while a persistent strengthening of the signal transmission is called long-term potentiation (LTP). These processes play distinct roles in the storage of spatial memories. The neuroscientists found that preventing Tamalin interactions with group 1 metabotropic glutamate receptors impaired LTD in the hippocampus. The other form of synaptic plasticity, LTP, was unaffected. The research group concludes from this observation that the interaction of Tamalin with group 1 metabotropic glutamate receptors is an important aspect of memory encoding by the hippocampus.
The German Research Foundation (DFG) supported the work within the Collaborative Research Centers SFB 874 and SFB 1280, which have been funded since 2010 and 2017 at the Ruhr-Universität Bochum.
Neyman S, Braunewell K-H, O´Connell K, Dev K, Manahan-Vaughan D (2019) Inhibition of the Interaction Between Group I Metabotropic Glutamate Receptors and PDZ-Domain Proteins Prevents Hippocampal Long-Term Depression, but Not Long-Term Potentiation. Frontiers in Synaptic Neuroscience, DOI: 10.3389/fnsyn.2019.00013
Link to the publication:
Prof. Dr Denise Manahan-Vaughan
Department of Neurophysiology
Faculty of Medicine
Phone: 0234 32 22042
Text: Judith Merkelt-Jedamzik
Translation: Judith Merkelt-Jedamzik