The physiological roles of phosducin: from retinal function to stress-dependent hypertension

Abstract

In the time since its discovery, phosducin's functions have been intensively studied both in vivo and in vitro. Phosducin's most important biochemical feature in in vitro studies is its binding to heterotrimeric G protein βγ-subunits. Data on phosducin's in vivo relevance, however, have only recently been published but expand the range of biological actions, as shown both in animal models as well as in human studies. This review gives an overview of different aspects of phosducin biology ranging from structure, phylogeny of phosducin family members, posttranscriptional modification, biochemical features, localization and levels of expression to its physiological functions. Special emphasis will be placed on phosducin's function in the regulation of blood pressure. In the second part of this article, findings concerning cardiovascular regulation and their clinical relevance will be discussed on the basis of recently published data from gene-targeted mouse models and human genetic studies.

Protein sorting, targeting and trafficking in photoreceptor cells

“…The significance of Gγ 1 farnesylation for Gβ 1 γ 1 translocation was revealed by demonstrating that a point mutation causing Gγ 1 to become geranylgeranylated instead leads to a major slowdown in Gβ 1 γ 1 translocation (Kassai et al, 2005). Another mechanism enhancing Gβ 1 γ 1 solubility is the binding to phosducin, a major photoreceptor-specific protein interacting with multiple types of G protein βγ-subunits (Beetz and Hein, 2011). Gβ 1 γ 1 binding to phosducin results in the insertion of the farnesyl moiety into a cleft formed between these two molecules (Loew et al, 1998), which makes the entire complex highly soluble (Yoshida et al, 1994).…”

G Protein‐Coupled Signal Transmission Pathways

“…Phosducin is an abundant protein in photoreceptor cells of the retina that is widely assumed to regulate light sensitivity through interaction with the bc-subunits of the visual G protein transducin [20]. Related proteins, the phosducin-like proteins, are found in other tissues, such as the brain and the pineal gland.…”

Phosducin Regulates Secretory Activity in TT Line of Thyroid Parafollicular C Cells

“…Phosducin, a 33-kDa cytoplasmic phosphoprotein found predominantly in photoreceptor cells, has been a subject of intense studies since the 1990s. Dephosphorylated phosducin interacts with the Gβ subunit of the G protein transducin, thereby precluding the formation of the Gαβγ heterotrimer and blocking the β subunit surface responsible for interaction with diverse effectors, which impairs signal generation by the Gβγ dimer [1][2][3]. Deletion of the phosducin gene in mice leads to stress-induced hypertension associated with faster repolarization of sympathetic neurons [2].…”

“…Dephosphorylated phosducin interacts with the Gβ subunit of the G protein transducin, thereby precluding the formation of the Gαβγ heterotrimer and blocking the β subunit surface responsible for interaction with diverse effectors, which impairs signal generation by the Gβγ dimer [1][2][3]. Deletion of the phosducin gene in mice leads to stress-induced hypertension associated with faster repolarization of sympathetic neurons [2]. This deletion also decreases the transducin βγ level [4], and impairs light signal transmission in the retina [5].…”