8.A.62 The Transmembrane and Ubiquitin-like domain-containing Protein 1 (Tmub1) Family
Some ubiquitin-like (UBL) domain-containing proteins play roles in receptor trafficking. Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs; TC# 1.A.10) undergo constitutive cycling between the intracellular compartment and the cell surface in the central nervous system. Yang et al. 2008 reported that the Tmub1 protein, formerly known as the Hepatocyte Odd Protein Shuttling (HOPS) protein, which is abundantly expressed in the brain and which exists in a synaptosomal membrane fraction, facilitates the recycling of the AMPAR subunit GluR2 to the cell surface. Neurons transfected with Tmub1/HOPS-RNAi plasmids showed a reduction in the AMPAR current as compared to control neurons. The synaptic surface expression of GluR2, but not of GluR1, was decreased in neurons transfected with the Tmub1/HOPS- RNAi and increased in neurons overexpressing EGFP-Tmub1/HOPS. The altered surface expression of GluR2 may be due to the altered surface-recycling of the internalized GluR2. GluR2 and the glutamate receptor interacting protein (GRIP) were coimmunoprecipitated by anti-Tmub1/HOPS antibody. Thus, Tmub1/HOPS plays a role in regulating basal synaptic transmission; it contributes to maintain the synaptic surface number of the GluR2-containing AMPARs by facilitating the recycling of GluR2 to the plasma membrane (Yang et al. 2008).