View source for Biology:Dystrophin-associated protein complex

The '''dystrophin-associated protein complex''', also known as the '''dystrophin-associated glycoprotein complex'''  is a multiprotein complex that includes [[Biology:Dystrophin|dystrophin]] and the [[Biology:Dystrophin-associated protein|dystrophin-associated protein]]s.<ref name="Charvet">{{cite journal | vauthors = Charvet B, Ruggiero F, Le Guellec D | title = The development of the myotendinous junction. A review | journal = Muscles, Ligaments and Tendons Journal | volume = 2 | issue = 2 | pages = 53–63 | date = April 2012 | pmid = 23738275 | pmc = 3666507 }}</ref> It is one of the two protein complexes that make up the [[Biology:Costamere|costamere]] in striated muscle cells. The other complex is the ''integrin-vinculin-talin complex''.
== Structure ==
The dystrophin-associated protein complex includes [[Biology:Dystrophin|dystrophin]].<ref name=":0">{{MeshName|Dystrophin-Associated+Protein+Complex}}</ref><ref name=":1">{{cite book | vauthors = Welling PA |title=CHAPTER 12 - Scaffolding Proteins in Transport Regulation|chapter=Scaffolding Proteins in Transport Regulation|date=2008-01-01 |work=Seldin and Giebisch's The Kidney (Fourth Edition)|pages=325–341| veditors = Alpern RJ, Herbert SC |place=San Diego|publisher=Academic Press|language=en|doi=10.1016/b978-012088488-9.50015-2|isbn=978-0-12-088488-9 }}</ref> Dystrophin binds to actin of the [[Biology:Cytoskeleton|cytoskeleton]], and also to proteins in the [[Biology:Extracellular matrix|extracellular matrix]].<ref name=":1" />

The dystrophin-associated protein complex also contains [[Biology:Dystrophin-associated protein|dystrophin-associated protein]]s.<ref name=":0" /> This includes a four subunit sarcoglycan complex, which is fixed to dystrophin in [[Biology:Muscle cell|muscle cell]]s.<ref>{{cite book | vauthors = Kirschner J, Lochmüller H | title = Muscular Dystrophies | chapter = Sarcoglycanopathies | series = Handbook of Clinical Neurology | volume = 101 | pages = 41–46 | date = 2011-01-01 | pmid = 21496623 | doi = 10.1016/b978-0-08-045031-5.00003-7 | publisher = Elsevier | isbn = 9780080450315 | veditors = Griggs RC, Amato AA }}</ref>

In the epithelia of the kidney, dystrophin may be replaced with [[Biology:Utrophin|utrophin]].<ref name=":1" />

[[Biology:Aquaporin 4|Aquaporin 4]] may be connected to the dystrophin-associated protein complex.<ref>{{cite book | vauthors = Binder DK |title=Chapter 17 - Water Homeostasis Dysfunction in Epilepsy|chapter=Water Homeostasis Dysfunction in Epilepsy|date=2017-01-01 |work=Brain Edema|pages=315–335| veditors = Badaut J, Plesnila N |place=San Diego|publisher=Academic Press|language=en|doi=10.1016/b978-0-12-803196-4.00017-5 |isbn=978-0-12-803196-4 }}</ref>

== Function ==
The dystrophin-associated protein complex is important for [[Biology:Cell biology|cell structure]] and [[Biology:Cell signaling|cell signalling]].<ref name=":1" /> It is one of two protein complexes found in the [[Biology:Costamere|costamere]] in striated muscle fibres.

== Clinical significance ==
Many forms of [[Medicine:Muscular dystrophy|muscular dystrophy]] are associated with disorders of the dystrophin-associated protein complex.<ref name="pmid12082140">{{cite journal | vauthors = Ehmsen J, Poon E, Davies K | title = The dystrophin-associated protein complex | journal = Journal of Cell Science | volume = 115 | issue = Pt 14 | pages = 2801–2803 | date = July 2002 | doi = 10.1242/jcs.115.14.2801 | pmid = 12082140 | url = http://jcs.biologists.org/cgi/pmidlookup?view=long&pmid=12082140 }}</ref>

Muscular dystrophy, the result of mutations in the genes that encode for dystrophin and the associated proteins that binds to it can arise in various forms.<ref name=":02">{{cite journal | vauthors = Lovering RM, Porter NC, Bloch RJ | title = The muscular dystrophies: from genes to therapies | journal = Physical Therapy | volume = 85 | issue = 12 | pages = 1372–1388 | date = December 2005 | doi = 10.1093/ptj/85.12.1372 | pmid = 16305275 | pmc = 4496952 }}</ref> The most common form is known as [[Medicine:Duchenne muscular dystrophy|Duchenne muscular dystrophy]] (DMD).<ref name=":12">{{cite journal | vauthors = Passamano L, Taglia A, Palladino A, Viggiano E, D'Ambrosio P, Scutifero M, Rosaria Cecio M, Torre V, DE Luca F, Picillo E, Paciello O, Piluso G, Nigro G, Politano L | display-authors = 6 | title = Improvement of survival in Duchenne Muscular Dystrophy: retrospective analysis of 835 patients | journal = Acta Myologica | volume = 31 | issue = 2 | pages = 121–125 | date = October 2012 | pmid = 23097603 | pmc = 3476854 }}</ref> DMD is usually discovered in early childhood and is most often seen occurring in males. There are several associated symptoms that can be observed in such patients including but not limited to a delay in walking and sitting, difficulty in breathing and heart failure.<ref>{{cite journal | vauthors = Gao QQ, McNally EM | title = The Dystrophin Complex: Structure, Function, and Implications for Therapy | journal = Comprehensive Physiology | volume = 5 | issue = 3 | pages = 1223–1239 | date = July 2015 | pmid = 26140716 | pmc = 4767260 | doi = 10.1002/cphy.c140048 | isbn = 9780470650714 }}</ref><ref>{{cite journal | vauthors = Ryder S, Leadley RM, Armstrong N, Westwood M, de Kock S, Butt T, Jain M, Kleijnen J | display-authors = 6 | title = The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review | journal = Orphanet Journal of Rare Diseases | volume = 12 | issue = 1 | pages = 79 | date = April 2017 | pmid = 28446219 | pmc = 5405509 | doi = 10.1186/s13023-017-0631-3 | doi-access = free }}</ref> These symptoms are found as a result of the inability to synthesize dystrophin and associate protein complexes that leave muscles weak and unable to repair any damaged sustained. These perpetually weak muscles prohibit normal physical activity.<ref name=":12" />

===Therapy===
There has been extensive research to discover treatment for DMD. The most common drug treated against DMD is known to be Deflazacort yielding the greatest benefits with the most acceptable side effects. Physical therapy consists of varying exercises that aim to increase muscle strength and durability so to facilitate normal physical activity and is recommended to begin as early as possible after diagnosis. Contracture intervention is recommended for patients in the middle ambulatory stage. However, surgical approach to DMD is declining as less invasive treatment becomes available. While treatment for DMD has been observed to improve muscle function and quality of life, a cure to the debilitating disease remains to be found.<ref name=":02" /><ref>{{cite journal | vauthors = Wagner KR, Lechtzin N, Judge DP | title = Current treatment of adult Duchenne muscular dystrophy | journal = Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | volume = 1772 | issue = 2 | pages = 229–237 | date = February 2007 | pmid = 16887341 | doi = 10.1016/j.bbadis.2006.06.009 | series = The Muscular Dystrophies: Molecular Basis and Therapeutic Strategies | doi-access = free }}</ref>

==Therapeutic Microdystrophin==
* [[Biology:Delandistrogene moxeparvovec|Delandistrogene moxeparvovec]] - Systemic Gene Transfer with [[Biology:Adeno-associated virus|rAAV]]rh74.MHCK7.micro-dystrophin.<ref>{{Cite web|url=https://www.chugai-pharm.co.jp/english/news/detail/20211216150001_885.html|title = Dec 16,2021 &#124; Chugai In-Licenses Gene Therapy Delandistrogene Moxeparvovec (SRP-9001) for Duchenne Muscular Dystrophy &#124; News}}</ref><ref>{{cite journal |last1=Mendell |first1=Jerry R. |last2=Sahenk |first2=Zarife |last3=Lehman |first3=Kelly |last4=Nease |first4=Carrie |last5=Lowes |first5=Linda P. |last6=Miller |first6=Natalie F. |last7=Iammarino |first7=Megan A. |last8=Alfano |first8=Lindsay N. |last9=Nicholl |first9=Amanda |last10=Al-Zaidy |first10=Samiah |last11=Lewis |first11=Sarah |last12=Church |first12=Kathleen |last13=Shell |first13=Richard |last14=Cripe |first14=Linda H. |last15=Potter |first15=Rachael A. |last16=Griffin |first16=Danielle A. |last17=Pozsgai |first17=Eric |last18=Dugar |first18=Ashish |last19=Hogan |first19=Mark |last20=Rodino-Klapac |first20=Louise R. |title=Assessment of Systemic Delivery of rAAVrh74.MHCK7.micro-dystrophin in Children With Duchenne Muscular Dystrophy: A Nonrandomized Controlled Trial |journal=JAMA Neurology |date=1 September 2020 |volume=77 |issue=9 |pages=1122–1131 |doi=10.1001/jamaneurol.2020.1484 |pmid=32539076 |pmc=7296461 |url=https://investorrelations.sarepta.com/static-files/ba326dff-2918-46bd-9a42-4ba73676a77f |access-date=9 November 2022 |language=en|doi-access=free }}</ref><ref>{{Cite web|url=https://adisinsight.springer.com/drugs/800050822|title=Delandistrogene moxeparvovec - Roche/Sarepta Therapeutics - AdisInsight|website=adisinsight.springer.com}}</ref>

== References ==
{{reflist}}


[[Category:Protein complexes]]



{{Sourceattribution|Dystrophin-associated protein complex}}