Submitted Successfully!
Thank you for your contribution! You can also upload a video entry related to this topic through the link below:
https://encyclopedia.pub/user/video_add?id=3856
Check Note
2000/2000
Ver. Summary Created by Modification Content Size Created at Operation
1 + 478 word(s) 478 2020-12-15 08:11:18

SH3 and cysteine rich domain 3: The STAC3 gene provides instructions for making a protein whose function is not completely understood.

  • genes
Information

1. Normal Function

The STAC3 gene provides instructions for making a protein whose function is not completely understood. It plays a role in muscles used for movement (skeletal muscles). For the body to move normally, skeletal muscles must tense (contract) and relax in a coordinated way. Muscle contractions are triggered by changes in the concentration of certain charged atoms (ions) in muscle cells. The STAC3 protein aids in the process that triggers the release of calcium ions within muscle cells to start (initiate) muscle contraction.

The STAC3 protein interacts with two structures in muscle cells that are critical for calcium ion flow, dihydropyridine receptor (DHPR) and ryanodine receptor 1 (RYR1). However, STAC3's role in this formation is unknown. RYR1 forms a channel (the RYR1 channel) through which calcium ions can flow. In response to certain signals, DHPR turns on (activates) the RYR1 channel, and the activated RYR1 channel releases calcium ions stored in structures inside muscle cells. The resulting increase in the calcium ion concentration within muscle cells stimulates muscles to contract, allowing the body to move. The process by which certain chemical signals trigger muscle contraction is called excitation-contraction (E-C) coupling.

2. Health Conditions Related to Genetic Changes

2.1. STAC3 disorder

At least five mutations in the STAC3 gene have been found to cause STAC3 disorder (formerly known as Native American myopathy). This condition is a muscle disorder characterized by weakness, droopy eyelids (ptosis) and other distinctive facial features, joint deformities (contractures), and increased risk of a condition known as malignant hyperthermia, which is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures.

Mutations in the STAC3 gene reduce the amount or impair the function of the STAC3 protein. Although the mechanism is unclear, studies show that a shortage of working STAC3 protein affects the function of DHPR and prevents the release of calcium ions by RYR1 channels, resulting in a buildup of calcium in storage. A disruption in calcium ion release prevents muscles from contracting normally, leading to the muscle weakness characteristic of STAC3 disorder.

It is unclear how these STAC3 gene mutations lead to malignant hyperthermia in susceptible individuals. Mutations in other genes related to malignant hyperthermia activate the RYR1 channel improperly in response to certain drugs. As a result, large amounts of calcium ions are released from storage within muscle cells. An overabundance of available calcium ions causes skeletal muscles to contract abnormally, which leads to muscle rigidity. An increase in calcium ion concentration also activates processes that generate heat (leading to increased body temperature) and produce excess acid (leading to acidosis). It is unknown if STAC3 gene mutations have a similar effect on RYR1 channel activity.

3. Other Names for This Gene

  • SH3 AND CYSTEINE-RICH DOMAINS 3

  • STAC3 gene

References

  1. Campiglio M, Costé de Bagneaux P, Ortner NJ, Tuluc P, Van Petegem F, FlucherBE. STAC proteins associate to the IQ domain of Ca(V)1.2 and inhibitcalcium-dependent inactivation. Proc Natl Acad Sci U S A. 2018 Feb6;115(6):1376-1381. doi: 10.1073/pnas.1715997115.
  2. Horstick EJ, Linsley JW, Dowling JJ, Hauser MA, McDonald KK, Ashley-Koch A,Saint-Amant L, Satish A, Cui WW, Zhou W, Sprague SM, Stamm DS, Powell CM, SpeerMC, Franzini-Armstrong C, Hirata H, Kuwada JY. Stac3 is a component of theexcitation-contraction coupling machinery and mutated in Native Americanmyopathy. Nat Commun. 2013;4:1952. doi: 10.1038/ncomms2952.
  3. Linsley JW, Hsu IU, Groom L, Yarotskyy V, Lavorato M, Horstick EJ, Linsley D, Wang W, Franzini-Armstrong C, Dirksen RT, Kuwada JY. Congenital myopathy results from misregulation of a muscle Ca2+ channel by mutant Stac3. Proc Natl Acad Sci US A. 2017 Jan 10;114(2):E228-E236. doi: 10.1073/pnas.1619238114.
  4. Polster A, Nelson BR, Olson EN, Beam KG. Stac3 has a direct role in skeletalmuscle-type excitation-contraction coupling that is disrupted by amyopathy-causing mutation. Proc Natl Acad Sci U S A. 2016 Sep27;113(39):10986-91. doi: 10.1073/pnas.1612441113.
  5. Polster A, Perni S, Bichraoui H, Beam KG. Stac adaptor proteins regulatetrafficking and function of muscle and neuronal L-type Ca2+ channels. Proc NatlAcad Sci U S A. 2015 Jan 13;112(2):602-6. doi: 10.1073/pnas.1423113112.
  6. Wong King Yuen SM, Campiglio M, Tung CC, Flucher BE, Van Petegem F. Structuralinsights into binding of STAC proteins to voltage-gated calcium channels. ProcNatl Acad Sci U S A. 2017 Nov 7;114(45):E9520-E9528. doi:10.1073/pnas.1708852114.
  7. Zaharieva IT, Sarkozy A, Munot P, Manzur A, O'Grady G, Rendu J, Malfatti E,Amthor H, Servais L, Urtizberea JA, Neto OA, Zanoteli E, Donkervoort S, Taylor J,Dixon J, Poke G, Foley AR, Holmes C, Williams G, Holder M, Yum S, Medne L,Quijano-Roy S, Romero NB, Fauré J, Feng L, Bastaki L, Davis MR, Phadke R, SewryCA, Bönnemann CG, Jungbluth H, Bachmann C, Treves S, Muntoni F. STAC3 variantscause a congenital myopathy with distinctive dysmorphic features and malignanthyperthermia susceptibility. Hum Mutat. 2018 Dec;39(12):1980-1994. doi:10.1002/humu.23635.
More
Information
Contributor :
View Times: 43
Entry Collection: MedlinePlus
Revision: 1 times (View History)
Update Time: 22 Dec 2020
Table of Contents

    Confirm

    Are you sure to Delete?

    Video Upload Options

    Do you have a full video?
    Cite
    If you have any further questions, please contact Encyclopedia Editorial Office.
    Liu, R. STAC3 Gene. Encyclopedia. Available online: https://encyclopedia.pub/entry/3856 (accessed on 15 August 2022).
    Liu R. STAC3 Gene. Encyclopedia. Available at: https://encyclopedia.pub/entry/3856. Accessed August 15, 2022.
    Liu, Rui. "STAC3 Gene," Encyclopedia, https://encyclopedia.pub/entry/3856 (accessed August 15, 2022).
    Liu, R. (2020, December 22). STAC3 Gene. In Encyclopedia. https://encyclopedia.pub/entry/3856
    Liu, Rui. ''STAC3 Gene.'' Encyclopedia. Web. 22 December, 2020.
    Share
    Download
    Cite
    Top