RGD Reference Report - UBXD4, a UBX-containing protein, regulates the cell surface number and stability of alpha3-containing nicotinic acetylcholine receptors. - Rat Genome Database

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UBXD4, a UBX-containing protein, regulates the cell surface number and stability of alpha3-containing nicotinic acetylcholine receptors.

Authors: Rezvani, K  Teng, Y  Pan, Y  Dani, JA  Lindstrom, J  Garcia Gras, EA  McIntosh, JM  De Biasi, M 
Citation: Rezvani K, etal., J Neurosci. 2009 May 27;29(21):6883-96. doi: 10.1523/JNEUROSCI.4723-08.2009.
RGD ID: 8554250
Pubmed: PMID:19474315   (View Abstract at PubMed)
PMCID: PMC2935801   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.4723-08.2009   (Journal Full-text)

Adaptor proteins are likely to modulate spatially and temporally the trafficking of a number of membrane proteins, including neuronal nicotinic acetylcholine receptors (nAChRs). A yeast two-hybrid screen identified a novel UBX-containing protein, UBXD4, as one of the cytosolic proteins that interact directly with the alpha3 and alpha4 nAChR subunits. The function of UBX-containing proteins is largely unknown. Immunoprecipitation and confocal microscopy confirmed the interaction of UBXD4 with alpha3-containing nAChRs (alpha3* nAChRs) expressed in HEK293 cells, PC12 cells, and rat cortical neurons. Overexpression of UBXD4 in differentiated PC12 cells (dPC12) increased nAChR cell surface expression, especially that of the alpha3beta2 subtype. These findings were corroborated by electrophysiology, immunofluorescent staining, and biotinylation of surface receptors. Silencing of UBXD4 led to a significant reduction of alpha3* nAChRs in rat cortical neurons and dPC12 cells. Biochemical and immunofluorescence studies of endogenous UBXD4 showed that the protein is located in both the ER and cis-Golgi compartments. Our investigations also showed that the alpha3 subunit is ubiquitinated and that UBXD4 can interfere with its ubiquitination and consequent degradation by the proteasome. Our data suggest that UBXD4 modulates the distribution of alpha3* nAChRs between specialized intracellular compartments and the plasma membrane. This effect is achieved by controlling the stability of the alpha3 subunit and, consequently, the number of receptors at the cell surface.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
regulation of gene expression acts_upstream_of_or_withinIMP 8554250PMID:19474315MGI 

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Canx  (calnexin)
Chrnb2  (cholinergic receptor nicotinic beta 2 subunit)
Chrnb4  (cholinergic receptor nicotinic beta 4 subunit)
Enpp1  (ectonucleotide pyrophosphatase/phosphodiesterase 1)
Golga2  (golgin A2)
Hspa5  (heat shock protein family A (Hsp70) member 5)
Kdelr1  (KDEL endoplasmic reticulum protein retention receptor 1)
Kdelr2  (KDEL endoplasmic reticulum protein retention receptor 2)
Lap3  (leucine aminopeptidase 3)
Lman1  (lectin, mannose-binding, 1)
Ubxn2a  (UBX domain protein 2A)


Additional Information