Journal
JOURNAL OF NEUROCHEMISTRY
Volume 122, Issue 1, Pages 24-37Publisher
WILEY
DOI: 10.1111/j.1471-4159.2012.07752.x
Keywords
26S proteasome; degradation; Homer protein; metabotropic glutamate receptor; protein trafficking; ubiquitin
Categories
Funding
- Alzheimer Research Trust
- Neurosciences Support Group at the Queen's Medical Centre (NSG@QMC)
- NIHR21 [1180103304]
- Divioson of Basic Biomemdcal Sciences of the University of South Dakota
- Alzheimers Research UK [ART-PG2001-1] Funding Source: researchfish
Ask authors/readers for more resources
J. Neurochem. (2012) 122, 2437. Abstract The metabotropic glutamate receptors (mGluRs) fine-tune the efficacy of synaptic transmission. This unique feature makes mGluRs potential targets for the treatment of various CNS disorders. There is ample evidence to show that the ubiquitin proteasome system mediates changes in synaptic strength leading to multiple forms of synaptic plasticity. The present study describes a novel interaction between post-synaptic adaptors, long Homer-3 proteins, and one of the 26S proteasome regulatory subunits, the S8 ATPase, that influences the degradation of the metabotropic glutamate receptor 1a (mGluR1a). We have shown that the two human long Homer-3 proteins specifically interact with human proteasomal S8 ATPase. We identified that mGluR1a and long Homer-3s immunoprecipitate with the 26S proteasome both in vitro and in vivo. We further found that the mGluR1a receptor can be ubiquitinated and degraded by the 26S proteasome and that Homer-3A facilitates this process. Furthermore, the siRNA mediated silencing of Homer-3 led to increased levels of total and plasma membrane-associated mGluR1a receptors. These results suggest that long Homer-3 proteins control the degradation of mGluR1a receptors by shuttling ubiquitinated mGluR-1a receptors to the 26S proteasome via the S8 ATPase which may modulate synaptic transmission.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available