Does the MK2-dependent production of TNFα regulate mGluR-dependent synaptic plasticity?

The molecular mechanisms and signalling cascades that trigger the induction of group I metabotropic glutamate receptor (GI-mGluR)-dependent long-term depression (LTD) have been the subject of intensive investigation for nearly two decades. The generation of genetically modified animals has played a crucial role in elucidating the involvement of key molecules regulating the induction and maintenance of mGluR-LTD. In this review we will discuss the requirement of the newly discovered MAPKAPK-2 (MK2) and MAPKAPK-3 (MK3) signalling cascade in regulating GI-mGluR-LTD. Recently, it has been shown that the absence of MK2 impaired the induction of GI-mGluR-dependent LTD, an effect that is caused by reduced internalization of AMPA receptors (AMPAR). As the MK2 cascade directly regulates tumour necrosis factor alpha (TNFα) production, this review will examine the evidence that the release of TNFα acts to regulate glutamate receptor expression and therefore may play a functional role in the impairment of GI-mGluRdependent LTD and the cognitive deficits observed in MK2/3 double knockout animals. The strong links of increased TNFα production in both aging and neurodegenerative disease could implicate the action of MK2 in these processes.

URI

http://hdl.handle.net/10454/8746

Version

Accepted manuscript

Citation

Hogg EL, Muller J and Correa SAL (2016) Does the MK2-dependent production of TNFα regulate mGluR-dependent synaptic plasticity? Current Neuropharmacology. 14(5): 474-480.

Link to Version of Record

https://doi.org/10.2174/1570159X13666150624165939

Type

Article