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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
2011-8-15
pubmed:abstractText
The key visual G protein, transducin undergoes bi-directional translocations between the outer segment (OS) and inner compartments of rod photoreceptors in a light-dependent manner thereby contributing to adaptation and neuroprotection of rods. A mammalian uncoordinated 119 protein (UNC119), also known as Retina Gene 4 protein (RG4), has been recently implicated in transducin transport to the OS in the dark through its interaction with the N-acylated GTP-bound transducin-? subunit (G?(t1)). Here, we demonstrate that the interaction of human UNC119 (HRG4) with transducin is dependent on the N-acylation, but does not require the GTP-bound form of G?(t1). The lipid specificity of UNC119 is unique: UNC119 bound the myristoylated N terminus of G?(t1) with much higher affinity than a prenylated substrate, whereas the homologous prenyl-binding protein PrBP/? did not interact with the myristoylated peptide. UNC119 was capable of interacting with G?(t1)GDP as well as with heterotrimeric transducin (G(t)). This interaction of UNC119 with G(t) led to displacement of G?(1)?(1) from the heterotrimer. Furthermore, UNC119 facilitated solubilization of G(t) from dark-adapted rod OS membranes. Consistent with these observations, UNC119 inhibited rhodopsin-dependent activation of G(t), but had no effect on the GTP-hydrolysis by G?(t1). A model for the role of UNC119 in the IS?OS translocation of G(t) is proposed based on the UNC119 ability to dissociate G(t) subunits from each other and the membrane. We also found that UNC119 inhibited activation of G(o) by D2 dopamine receptor in cultured cells. Thus, UNC119 may play conserved inhibitory role in regulation of GPCR-G protein signaling in non-visual tissues.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
28954-62
pubmed:dateRevised
2011-10-19
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Interaction of transducin with uncoordinated 119 protein (UNC119): implications for the model of transducin trafficking in rod photoreceptors.
pubmed:affiliation
Department of Molecular Physiology and Biophysics, University of Iowa, Iowa City, Iowa 52242, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural