Arrestin: Difference between revisions

Revision as of 17:54, 11 February 2025

A family of proteins involved in signal transduction

Arrestins are a family of proteins that play a crucial role in the regulation of G protein-coupled receptors (GPCRs). These proteins are involved in the desensitization of GPCRs, which are responsible for transmitting signals from the outside of a cell to the inside. Arrestins bind to phosphorylated receptors, preventing further signaling and facilitating receptor internalization.

Structure

Arrestins are composed of two main domains: the N-domain and the C-domain. These domains are connected by a flexible hinge region, allowing arrestins to undergo conformational changes necessary for their function. The structure of arrestins enables them to interact with both the phosphorylated receptor and other proteins involved in signal transduction.

Types of Arrestins

There are four known types of arrestins in mammals:

Visual arrestins: These include arrestin-1 and arrestin-4, which are primarily found in the retina and are involved in the desensitization of rhodopsin, a light-sensitive receptor.
Non-visual arrestins: Arrestin-2 and arrestin-3, also known as _-arrestin-1 and _-arrestin-2, are ubiquitously expressed and regulate a wide variety of GPCRs throughout the body.

Function

Arrestins perform several key functions in cellular signaling:

Desensitization: By binding to phosphorylated GPCRs, arrestins prevent further activation of G proteins, effectively desensitizing the receptor.
Internalization: Arrestins facilitate the internalization of GPCRs by linking them to clathrin and adaptor protein 2, leading to receptor endocytosis.
Signaling: Beyond desensitization, arrestins can initiate alternative signaling pathways by acting as scaffolds for other signaling proteins, such as MAP kinase pathways.

Role in Disease

Dysregulation of arrestin function has been implicated in various diseases. For example, mutations in visual arrestins can lead to retinal degenerative diseases, while altered expression of non-visual arrestins has been associated with cancer and cardiovascular diseases.

Research and Therapeutic Potential

Arrestins are a focus of research due to their role in GPCR signaling, which is a target for many pharmaceuticals. Understanding arrestin function can lead to the development of drugs that specifically modulate arrestin-mediated pathways, offering potential therapeutic benefits.

Related pages

Gallery

Apple Mail

Apple Mail

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-'''Arrestin''' is a [[protein]] that plays a significant role in regulating [[signal transduction]] at [[G protein-coupled receptors]]. There are four known arrestin subtypes in mammals. Two are ubiquitously expressed and are known as [[beta-arrestin 1]] and [[beta-arrestin 2]], which are also called arrestin 2 and arrestin 3, respectively. The other two are expressed mainly in the [[neurons]] of the [[visual system]] and are known as [[arrestin 1]] (or visual arrestin, S-antigen) and [[arrestin 4]] (or cone arrestin, X-arrestin).
+{{Short description|A family of proteins involved in signal transduction}}
+{{Use dmy dates|date=October 2023}}
-== Function ==
+'''Arrestins''' are a family of proteins that play a crucial role in the regulation of [[G protein-coupled receptors]] (GPCRs). These proteins are involved in the desensitization of GPCRs, which are responsible for transmitting signals from the outside of a cell to the inside. Arrestins bind to phosphorylated receptors, preventing further signaling and facilitating receptor internalization.
-Arrestins bind to the [[G protein-coupled receptor]] (GPCR) and [[desensitize]] it, preventing the receptor from activating additional [[G protein]]s, thus terminating the signal. Arrestins also serve to [[internalize]] the GPCR, acting as an adapter protein to aid in the receptor's endocytosis.
-== Structure ==
+==Structure==
-Arrestins are elongated molecules. The N- and C-domains, which are similar in structure, are each composed of a seven-strand [[beta-sandwich]] flanked by two [[alpha-helix|alpha-helices]]. The two domains are connected by a 12-residue polar [[core]], which is thought to be crucial for the activation of arrestin.
+Arrestins are composed of two main domains: the N-domain and the C-domain. These domains are connected by a flexible hinge region, allowing arrestins to undergo conformational changes necessary for their function. The structure of arrestins enables them to interact with both the phosphorylated receptor and other proteins involved in signal transduction.
-== Clinical significance ==
+==Types of Arrestins==
-Mutations in the arrestin genes have been associated with a number of diseases, including [[night blindness]] and [[Oguchi disease]]. In addition, arrestins have been implicated in the development of [[heart failure]] and [[cancer]].
+There are four known types of arrestins in mammals:
-== See also ==
+* '''Visual arrestins''': These include arrestin-1 and arrestin-4, which are primarily found in the [[retina]] and are involved in the desensitization of [[rhodopsin]], a light-sensitive receptor.
+* '''Non-visual arrestins''': Arrestin-2 and arrestin-3, also known as _-arrestin-1 and _-arrestin-2, are ubiquitously expressed and regulate a wide variety of GPCRs throughout the body.
+==Function==
+Arrestins perform several key functions in cellular signaling:
+* '''Desensitization''': By binding to phosphorylated GPCRs, arrestins prevent further activation of [[G proteins]], effectively desensitizing the receptor.
+* '''Internalization''': Arrestins facilitate the internalization of GPCRs by linking them to [[clathrin]] and [[adaptor protein 2]], leading to receptor endocytosis.
+* '''Signaling''': Beyond desensitization, arrestins can initiate alternative signaling pathways by acting as scaffolds for other signaling proteins, such as [[MAP kinase]] pathways.
+==Role in Disease==
+Dysregulation of arrestin function has been implicated in various diseases. For example, mutations in visual arrestins can lead to retinal degenerative diseases, while altered expression of non-visual arrestins has been associated with cancer and cardiovascular diseases.
+==Research and Therapeutic Potential==
+Arrestins are a focus of research due to their role in GPCR signaling, which is a target for many pharmaceuticals. Understanding arrestin function can lead to the development of drugs that specifically modulate arrestin-mediated pathways, offering potential therapeutic benefits.
+==Related pages==
 * [[G protein-coupled receptor]]
 * [[Signal transduction]]
-* [[Beta-arrestin]]
+* [[Rhodopsin]]
+* [[Clathrin-mediated endocytosis]]
-== References ==
+==Gallery==
-<references />
+<gallery>
+File:Apple_Mail.png|Apple Mail
-== External links ==
+</gallery>
-* [https://www.ncbi.nlm.nih.gov/gene/408 Arrestin] at the US National Library of Medicine [[Medical Subject Headings]] (MeSH)
+[[Category:Signal transduction]]
 [[Category:Proteins]]
-[[Category:Signal transduction]]
-[[Category:Cell biology]]
-{{stub}}