Identification of the Gβ5-RGS7 Protein Complex in the Retina

Cabrera, Jorge L.; Freitas, Fatima de; Satpaev, Daulet K.; Slepak, Vladlen Z.

doi:10.1006/bbrc.1998.9218

Cited by 124 publications

(104 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since most of the RGS residues in direct contact with G ␣ are well conserved across the entire family, these residues are unlikely to determine RGS-G protein specificity alone. Rather, additional regulatory proteins, such as effectors (11), G␤ proteins (9,(35)(36)(37)(38), or G proteincoupled receptors (7,39) may be involved. Since five classspecific residues (r77, r117, r121, r122, r124, and r125) cluster above the RGS-G ␣ interface to form an active site common to all members of the family, a reasonable hypothesis is that this is the binding site for additional proteins that mediate specificity (Fig.…”

Section: Discussion Evolutionary Analysis Can Provide Insight Into Rgmentioning

confidence: 99%

A regulator of G protein signaling interaction surface linked to effector specificity

Sowa

Wensel

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Proteins of the regulator of G protein signaling (RGS) family accelerate GTP hydrolysis by the ␣ subunits (G␣) of G proteins, leading to rapid recovery of signaling cascades. Many different RGS proteins can accelerate GTP hydrolysis by an individual G ␣, and GTP hydrolysis rates of different G ␣s can be enhanced by the same RGS protein. Consequently, the mechanisms for specificity in RGS regulation and the residues involved remain unclear. Using the evolutionary trace (ET) method, we have identified a cluster of residues in the RGS domain that includes the RGS-G ␣ binding interface and extends to include additional functionally important residues on the surface. One of these is within helix ␣3, two are in ␣5, and three are in the loop connecting ␣5 and ␣6. A cluster of surface residues on G␣ previously identified by ET, and composed predominantly of residues from the switch III region and helix ␣3, is spatially contiguous with the ET-identified residues in the RGS domain. This cluster includes residues proposed to interact with the ␥ subunit of Gt␣'s effector, cGMP phosphodiesterase (PDE␥). The proximity of these clusters suggests that they form part of an interface between the effector and the RGS-G ␣ complex. Sequence variations in these residues correlate with PDE␥ effects on GTPase acceleration. Because ET identifies residues important for all members of a protein family, these residues likely form a general site for regulation of G protein-coupled signaling cascades, possibly by means of effector interactions.H eterotrimeric G proteins (G ␣␤␥ ) mediate a ubiquitous eukaryotic pathway that converts extracellular signals received by transmembrane serpentine receptors into changes in the concentrations of intracellular ions and small molecule second messengers, thereby controlling vision, cardiac function, and many aspects of neuroendocrine signaling. Upon activation, a receptor catalyzes the exchange of GDP for GTP in the ␣ subunit of a specific G protein (G ␣ ), and either G ␣-GTP or its G ␤␥ partner can interact with a membrane-bound downstream effector protein, leading to amplification of the initial signal. Essential to G protein signaling is the intrinsic temporal regulation of the cascade imposed by G ␣ 's ability to switch back to its inactive form through hydrolysis of GTP. The regulator of G protein signaling (RGS) family of proteins plays a critical role in this process by increasing the intrinsic GTP hydrolysis rate of G ␣ (1-4) and accelerating recovery of the system. Nearly 50 different RGS family members have been identified in eukaryotes thus far, ranging from yeast to humans; and in mammals, individual RGS proteins display distinct expression patterns. However, in general, different types of RGS proteins coexist with a variety of G proteins, leading to the question of how RGS-G ␣ specificity is maintained (5). The crystal structure of the RGS4-G i␣1 complex (6) reveals that the contact residues between the RGS domain and G ␣ are highly conserved in both proteins, implying that in situ RGS-G pr...

show abstract

Section: Discussion Evolutionary Analysis Can Provide Insight Into Rgmentioning

confidence: 99%

A regulator of G protein signaling interaction surface linked to effector specificity

Sowa

Wensel

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…A milestone in understanding the biology of R7 proteins was the discovery that they all exist as constitutive complexes with G␤5 (15,(27)(28)(29). G␤5 determines the folding and stability of R7 proteins and regulates their catalytic activity (reviewed in Ref.…”

Section: Novel Interacting Partner Of R7 Rgs Proteins 5135mentioning

confidence: 99%

R7BP, a Novel Neuronal Protein Interacting with RGS Proteins of the R7 Family

Martemyanov

Yoo

Skiba

et al. 2005

Journal of Biological Chemistry

136

192

View full text Add to dashboard Cite

The R7 subfamily of the regulators of G protein signaling (RGS) proteins is represented by four members broadly expressed in the mammalian nervous system. Here we report that in the brain all four R7 proteins form tight complexes with a previously unidentified protein, which we call the R7-binding protein or R7BP. We initially identified R7BP as a protein co-precipitating with the R7 protein, RGS9, from extracts obtained from the striatal region of the brain. We further showed that R7BP forms a tight complex with RGS9 in vitro and that this binding occurs via the N-terminal DEP domain of RGS9. R7BP is expressed throughout the entire central nervous system but not in any of the tested nonneuronal tissues. All four R7 RGS proteins co-precipitate with R7BP from brain extracts and recombinant R7 proteins bind recombinant R7BP with high efficiency. The closest homolog of R7BP is R9AP which was previously found to interact with RGS9 in photoreceptors. Both R7BP and R9AP are related to the syntaxin subfamily of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins involved in vesicular trafficking and exocytosis. In photoreceptors R9AP regulates several critical properties of RGS9 including its intracellular targeting, stability and catalytic activity. This suggests that R7BP interactions with R7 proteins in the brain may also bear major functional significance. RGS1 proteins regulate the duration of G protein signaling by stimulating the rate of the GTP hydrolysis on G protein ␣ subunits (reviewed in Refs. 1 and 2). RGS proteins are classified in six to nine subfamilies based on the homology within the RGS catalytic domain (1-3). Most RGS proteins contain additional noncatalytic domains that modulate the properties of their catalytic domains and allow them to interact with their partners in a broad range of signaling pathways. The R7 (also called "C") subfamily of RGS proteins contains four members expressed in the mammalian nervous system, RGS6, RGS7, RGS9, and RGS11 (reviewed in Ref. 4). R7 proteins share common domain composition and exist as constitutive complexes with the type 5 G protein ␤ subunit (G␤5).Marked progress in the understanding of the function of the R7 protein came from the studies of the short splice variant of RGS9, RGS9-1, which regulates signal duration in the phototransduction pathway in vertebrate rod and cone photoreceptors. Several functional properties of RGS9-1 in photoreceptors are regulated by its interacting partner, a SNARE-like protein R9AP. R9AP is responsible for targeting RGS9-1 to the photoreceptor outer segment, an intracellular compartment where phototransduction takes place (5). It also determines the RGS9-1 expression level by protecting RGS9-1 from proteolytic degradation in the cell (6). Finally, R9AP enhances the ability of RGS9-1 to stimulate G protein GTPase activity thus allowing the visual signal to be terminated on the physiologically rapid time scale (5,7,8). RGS9-1 interaction with R9AP is mediated by the N-terminal domain of RGS9-1 c...

show abstract

“…Perhaps most significantly, ␥-subunits determine the subcellular distribution of the G␤␥ complex because isoprenylation of the COOH-terminal of G␥s targets G␤␥ to the membrane (Muntz et al 1992). Interestingly, a G␥-like-domain (GGL) has been found in a subgroup of mammalian RGSs, indicating that ␤-subunits can also have additional partners in the cytosol (Cabrera et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

Gγ inDictyostelium: Its Role in Localization of Gβγ to the Membrane Is Required for Chemotaxis in Shallow Gradients

Zhang

Lan

Devreotes

2001

MBoC

View full text Add to dashboard Cite

Monitoring Editor: Joan S. Brugge G-protein-mediated signal transduction pathways play an essential role in the developmental program of the simple eukaryotic organism Dictyostelium discoideum. Database searches have yielded 11 G␣-subunits, a single G␤-subunit, but no G␥-subunits. We report here the purification, cDNA isolation, and functional analysis of a G␥-subunit. Like G␤, the G␥ appears to be unique and hybridization studies show that G␥ and G␤ are expressed in parallel during development. Species-wide sequence comparisons of G␥-subunits and ␥-like domains of RGS proteins reveal short stretches of highly conserved residues as well as the common CXXL motif at the COOHterminal of G␥s that target G␤␥s to plasma membrane. Overexpression of a CSVL-deleted G␥ (G␥⌬) in wild-type cells shifts G␤␥ to the cytosol and selectively impairs certain G-proteinmediated signal transduction pathways. These cells are able to respond to increments in the stimulus, but are unable to sense chemoattractant gradients. They neither move directionally nor recruit PH-domains to their leading edge. Thus, a full complement of membrane-tethered G␤␥ is required for sensing shallow gradients, but is not essential for responses to increments in extracellular stimuli.

show abstract

Identification of the Gβ5-RGS7 Protein Complex in the Retina

Cited by 124 publications

References 28 publications

A regulator of G protein signaling interaction surface linked to effector specificity

A regulator of G protein signaling interaction surface linked to effector specificity

R7BP, a Novel Neuronal Protein Interacting with RGS Proteins of the R7 Family

Gγ inDictyostelium: Its Role in Localization of Gβγ to the Membrane Is Required for Chemotaxis in Shallow Gradients

Contact Info

Product

Resources

About