Akuaporin 4

AQP4
Struktur yang tersedia
PDB	Pencarian Ortolog: PDBe RCSB
Daftar kode id PDB
	3GD8
Pengidentifikasi
Alias	AQP4, aquaporin 4, HMIWC2, MIWC, WCH4, hAQP4
ID eksternal	OMIM: 600308 MGI: 107387 HomoloGene: 37507 GeneCards: AQP4
Lokasi gen (Tikus)
Kr.	Kromosom 18 (tikus)
Akhir	15,544,039 bp
Ontologi gen
Fungsi molekuler	• aktivitas saluran air; • aktivitas transporter transmembran air; • GO:0001948, GO:0016582 Ikatan protein plasma; • pengikatan protein identik; • aktivitas saluran;
Komponen seluler	• sitoplasma; • komponen integral membran; • Membran sel; • membran plasma basolateral; • membran; • external side of plasma membrane; • integral component of plasma membrane; • Sarkolema; • astrocyte end-foot; • extracellular region; • endosom; • endosome membrane; • cell projection;
Proses biologis	• transpor air; • ion transmembrane transport; • multicellular organismal water homeostasis; • renal water homeostasis; • cellular response to interferon-gamma; • transpor transmembran; • cellular water homeostasis; • water homeostasis; • protein homotetramerization; • cerebrospinal fluid circulation;
	Sumber:Amigo / QuickGO
Ortolog
	361
	11829
	ENSG00000171885
	ENSMUSG00000024411
	P55087
	P55088
NM_001650; NM_004028; NM_001317384; NM_001317387; NM_001364286;
	NM_001364287; NM_001364289
NM_009700; NM_001308641; NM_001308642; NM_001308643; NM_001308644;
	NM_001308645; NM_001308646; NM_001308647; NM_001317729
NP_001304313; NP_001304316; NP_001641; NP_004019; NP_001351215;
	NP_001351216; NP_001351218
NP_001295570; NP_001295571; NP_001295572; NP_001295573; NP_001295574;
	NP_001295575; NP_001295576; NP_001304658; NP_033830
	Wikidata
Lihat/Sunting Manusia	Lihat/Sunting Tikus

Akuaporin-4, juga dikenal sebagai AQP4, adalah protein saluran air yang dikodekan oleh gen AQP4 pada manusia.^[4] AQP4 termasuk ke dalam famili protein membran integral akuaporin yang menyalurkan air melewati membran sel. Akuaporin dengan jumlah terbatas ditemukan di dalam sistem saraf pusat: AQP1, 3, 4, 5, 8, 9, dan 11, tetapi representasi yang lebih khusus dari AQP1, 4, dan 9 ditemukan di dalam otak dan sumsum tulang belakang.^[5] Pada sistem saraf pusat, AQP4 merupakan saluran akuaporin yang paling banyak ditemukan, secara spesifik terletak di astrosit tepi pembuluh mikro cuar kaki, pembatas glia, dan ependima.^[6]

Akuaporin-4 pertama kali diidentifikasi pada 1986. Protein ini merupakan bukti pertama dari keberadaan saluran transpor air.^[7] Metode yang digunakan untuk menemukan keberadaan saluran transpor ini adalah dengan eksperimen knockout. Dengan teknik ini, mereka dapat menunjukkan peran penting AQP4 pada kerusakan sistem saraf pusat dan ketakseimbangan air pada otak.^[5]

Struktur[sunting | sunting sumber]

Struktur AQP4 terdiri dari enam domain transmembran dan lima gelung penghubung membentuk saluran. Melalui kristalografi sinar-X, ditemukan bahwa “setiap monomer AQP4 memuat enam domain heliks berentang membran dan dua segmen heliks pendek melingkupi pori air sempit.”^[8] Serupa dengan saluran akuaporin lainnya, monomer AQP4 bergabung membentuk tetramer.^[9] Lebih lanjut, AQP4 memiliki dua bentuk isomer struktural berbeda yang terletak di sistem saraf pusat: M1 dan M23.^[5] Keduanya membentuk homotetramer dan heterotetramer yang permeabel terhadap air.^[5] Bentuk isomer M23 berupa susunan bujur sangkar lebih besar pada membran astrosit ujung akson, dibandingkan dengan bentuk isomer M1 yang lebih kecil dan takstabil. Tetramer akuaporin-4 berkumpul membentuk susunan partikel ortogonal (OAP) pada membran plasma sel.^[8]

Fungsi[sunting | sunting sumber]

Fungsi secara keseluruhan akuaporin-4 adalah menyediakan transportasi air dengan cepat seperti menjaga keseimbangan homeostatik di dalam sistem saraf pusat. Protein ini merupakan protein saluran air primer yang menyesuaikan homeostasis air di sistem saraf pusat.^[5] AQP4 mungkin terlibat dalam berbagai proses fisiologis seperti pembuangan sampah (sistem glimfatik) dan penyelarasan halus homeostasis kalium.^[10] Air mengalir ke dalam dan luar otak atau sumsum tulang belakang dibantu AQP4.^[5] Di sini, saluran AQP4 merespons secara pasif terhadap gradien osmotik. Lebih lanjut, AQP4 memainkan peran pada transpor air otak, migrasi sel, edema otak, metabolisme, dan homeostasis sel.^[11]

Sistem lainnya juga diregulasi oleh AQP4. Pada telinga dalam, peran utama AQP4 adalah memelihara keseimbangan osmotik dalam membantu sel epitelium di dalam organ Korti dengan mendaur ulang K⁺.^[7] Peran spesifik AQP4 lainnya adalah membantu molekul bau berikatan dengan reseptor target dan protein pengikat di dalam epitelium olfaktori.^[7] Di dalam retina, peran AQP-4 adalah untuk menjaga homeostasis.^[7] Akuaporin-4 penting dalam pembentukan memori maupun plastisitas sinapsis.^[10] Kinerja lainnya adalah akuaporin-4 terlibat pada plastisitas sinapsis, migrasi astrosit, regulasi volume ruang ekstraseluler, dan homeostasis kalium.^[10]

Referensi[sunting | sunting sumber]

^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000024411 - Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM, Agre P (December 1994). "Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance". Proceedings of the National Academy of Sciences of the United States of America. 91 (26): 13052–6. doi:10.1073/pnas.91.26.13052. PMC 45579 . PMID 7528931.
^ ^a ^b ^c ^d ^e ^f Oklinski MK, Skowronski MT, Skowronska A, Rützler M, Nørgaard K, Nieland JD, Kwon TH, Nielsen S (December 2016). "Aquaporins in the Spinal Cord". International Journal of Molecular Sciences. 17 (12): 2050. doi:10.3390/ijms17122050. PMC 5187850 . PMID 27941618.
^ Saadoun S, Papadopoulos MC (July 2010). "Aquaporin-4 in brain and spinal cord oedema". Neuroscience. 168 (4): 1036–46. doi:10.1016/j.neuroscience.2009.08.019. PMID 19682555.
^ ^a ^b ^c ^d Gleiser C, Wagner A, Fallier-Becker P, Wolburg H, Hirt B, Mack AF (August 2016). "Aquaporin-4 in Astroglial Cells in the CNS and Supporting Cells of Sensory Organs-A Comparative Perspective". International Journal of Molecular Sciences. 17 (9): 1411. doi:10.3390/ijms17091411. PMC 5037691 . PMID 27571065.
^ ^a ^b Verkman AS, Phuan PW, Asavapanumas N, Tradtrantip L (November 2013). "Biology of AQP4 and anti-AQP4 antibody: therapeutic implications for NMO". Brain Pathology. 23 (6): 684–95. doi:10.1111/bpa.12085. PMC 3890327 . PMID 24118484.
^ Chu H, Huang C, Ding H, Dong J, Gao Z, Yang X, Tang Y, Dong Q (August 2016). "Aquaporin-4 and Cerebrovascular Diseases". International Journal of Molecular Sciences. 17 (8): 1249. doi:10.3390/ijms17081249. PMC 5000647 . PMID 27529222.
^ ^a ^b ^c Hubbard JA, Szu JI, Binder DK (March 2017). "The role of aquaporin-4 in synaptic plasticity, memory and disease". Brain Research Bulletin. 17: 118–129. doi:10.1016/j.brainresbull.2017.02.011. PMID 28274814.
^ Desai, Bhargav; Hsu, Ying; Schneller, Benjamin; Hobbs, Johnathan G.; Mehta, Ankit I.; Linninger, Andreas (Summer 2016). "Hydrocephalus: the role of cerebral aquaporin-4 channels and computational modeling considerations of cerebrospinal fluid". Neurological Focus. 41 (3): 1–17. doi:10.3171/2016.7.FOCUS16191. PMID 27581320.

Bacaan lanjutan[sunting | sunting sumber]

Strand L, Moe SE, Solbu TT, Vaadal M, Holen T (June 2009). "Roles of aquaporin-4 isoforms and amino acids in square array assembly". Biochemistry. 48 (25): 5785–93. doi:10.1021/bi802231q. PMID 19445480.
Wu H, Zhang Z, Li Y, Zhao R, Li H, Song Y, Qi J, Wang J (October 2010). "Time course of upregulation of inflammatory mediators in the hemorrhagic brain in rats: correlation with brain edema". Neurochemistry International. 57 (3): 248–53. doi:10.1016/j.neuint.2010.06.002. PMC 2910823 . PMID 20541575.
Goodyear MJ, Crewther SG, Junghans BM (2009). "A role for aquaporin-4 in fluid regulation in the inner retina". Visual Neuroscience. 26 (2): 159–65. doi:10.1017/S0952523809090038. PMID 19366470.
Matsushita T, Matsuoka T, Isobe N, Kawano Y, Minohara M, Shi N, Nishimura Y, Ochi H, Kira J (February 2009). "Association of the HLA-DPB1*0501 allele with anti-aquaporin-4 antibody positivity in Japanese patients with idiopathic central nervous system demyelinating disorders". Tissue Antigens. 73 (2): 171–6. doi:10.1111/j.1399-0039.2008.01172.x. PMID 19140826.
Rubino E, Rainero I, Vaula G, Crasto F, Gravante E, Negro E, Brega F, Gallone S, Pinessi L (April 2009). "Investigating the genetic role of aquaporin4 gene in migraine". The Journal of Headache and Pain. 10 (2): 111–4. doi:10.1007/s10194-009-0100-z. PMC 3451641 . PMID 19209385.
Benarroch EE (December 2007). "Aquaporin-4, homeostasis, and neurologic disease". Neurology. 69 (24): 2266–8. doi:10.1212/01.wnl.0000286385.59836.e2. PMID 18071147.
Ho JD, Yeh R, Sandstrom A, Chorny I, Harries WE, Robbins RA, Miercke LJ, Stroud RM (May 2009). "Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductance". Proceedings of the National Academy of Sciences of the United States of America. 106 (18): 7437–42. doi:10.1073/pnas.0902725106. PMC 2678640 . PMID 19383790.
Assereto S, Mastrototaro M, Stringara S, Gazzerro E, Broda P, Nicchia GP, Svelto M, Bruno C, Nigro V, Lisanti MP, Frigeri A, Minetti C (July 2008). "Aquaporin-4 expression is severely reduced in human sarcoglycanopathies and dysferlinopathies". Cell Cycle. 7 (14): 2199–207. doi:10.4161/cc.7.14.6272. PMID 18641458.
Dibas A, Yang MH, He S, Bobich J, Yorio T (September 2008). "Changes in ocular aquaporin-4 (AQP4) expression following retinal injury". Molecular Vision. 14: 1770–83. PMC 2559817 . PMID 18836575.
Sorani MD, Zador Z, Hurowitz E, Yan D, Giacomini KM, Manley GT (August 2008). "Novel variants in human Aquaporin-4 reduce cellular water permeability". Human Molecular Genetics. 17 (15): 2379–89. doi:10.1093/hmg/ddn138. PMC 2733814 . PMID 18511455.
Ng WH, Hy JW, Tan WL, Liew D, Lim T, Ang BT, Ng I (March 2009). "Aquaporin-4 expression is increased in edematous meningiomas". Journal of Clinical Neuroscience. 16 (3): 441–3. doi:10.1016/j.jocn.2008.04.028. PMID 19153045.
Nishiyama S, Ito T, Misu T, Takahashi T, Kikuchi A, Suzuki N, Jin K, Aoki M, Fujihara K, Itoyama Y (June 2009). "A case of NMO seropositive for aquaporin-4 antibody more than 10 years before onset". Neurology. 72 (22): 1960–1. doi:10.1212/WNL.0b013e3181a82621. PMID 19487655.
Misu T, Fujihara K, Itoyama Y (May 2008). "[Neuromyelitis optica and anti-aquaporin 4 antibody--an overview]". Brain and Nerve = Shinkei Kenkyu No Shinpo (dalam bahasa Japanese). 60 (5): 527–37. PMID 18516975.
Dibas AI, Mia AJ, Yorio T (December 1998). "Aquaporins (water channels): role in vasopressin-activated water transport". Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine. 219 (3): 183–99. doi:10.3181/00379727-219-44332. PMID 9824541.
Doi H, Matsushita T, Isobe N, Matsuoka T, Minohara M, Ochi H, Kira JI (March 2009). "Hypercomplementemia at relapse in patients with anti-aquaporin-4 antibody". Multiple Sclerosis. 15 (3): 304–10. doi:10.1177/1352458508099139. PMID 19028829.
Pittock SJ, Lennon VA (May 2008). "Aquaporin-4 autoantibodies in a paraneoplastic context". Archives of Neurology. 65 (5): 629–32. doi:10.1001/archneur.65.5.629. PMID 18474738.
Matsushita T, Isobe N, Matsuoka T, Shi N, Kawano Y, Wu XM, Yoshiura T, Nakao Y, Ishizu T, Kira JI (July 2009). "Aquaporin-4 autoimmune syndrome and anti-aquaporin-4 antibody-negative opticospinal multiple sclerosis in Japanese". Multiple Sclerosis. 15 (7): 834–47. doi:10.1177/1352458509104595. PMID 19465451.
Graber DJ, Levy M, Kerr D, Wade WF (May 2008). "Neuromyelitis optica pathogenesis and aquaporin 4". Journal of Neuroinflammation. 5: 22. doi:10.1186/1742-2094-5-22. PMC 2427020 . PMID 18510734.
Baba T, Nakashima I, Kanbayashi T, Konno M, Takahashi T, Fujihara K, Misu T, Takeda A, Shiga Y, Ogawa H, Itoyama Y (February 2009). "Narcolepsy as an initial manifestation of neuromyelitis optica with anti-aquaporin-4 antibody". Journal of Neurology. 256 (2): 287–8. doi:10.1007/s00415-009-0139-4. PMID 19266146.
Xu H, Zhang Y, Wei W, Shen L, Wu W (January 2009). "Differential expression of aquaporin-4 in human gastric normal and cancer tissues". Gastroenterologie Clinique et Biologique. 33 (1 Pt 1): 72–6. doi:10.1016/j.gcb.2008.07.010. PMID 19112001.
Kadohira I, Abe Y, Nuriya M, Sano K, Tsuji S, Arimitsu T, Yoshimura Y, Yasui M (December 2008). "Phosphorylation in the C-terminal domain of Aquaporin-4 is required for Golgi transition in primary cultured astrocytes". Biochemical and Biophysical Research Communications. 377 (2): 463–8. doi:10.1016/j.bbrc.2008.09.155. PMID 18854171.

Pranala luar[sunting | sunting sumber]

MeSH Aquaporin+4
Lokasi genom AQP4 manusia dan halaman rincian gen AQP4 dalam UCSC Genome Browser.

[refGRCm38Ensembl-1] GRCm38: Ensembl release 89: ENSMUSG00000024411 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Jung-4] Jung JS, Bhat RV, Preston GM, Guggino WB, Baraban JM, Agre P (December 1994). "Molecular characterization of an aquaporin cDNA from brain: candidate osmoreceptor and regulator of water balance". Proceedings of the National Academy of Sciences of the United States of America. 91 (26): 13052–6. doi:10.1073/pnas.91.26.13052. PMC 45579 . PMID 7528931.

[Oklinski_2016-5] ^ ^a ^b ^c ^d ^e ^f Oklinski MK, Skowronski MT, Skowronska A, Rützler M, Nørgaard K, Nieland JD, Kwon TH, Nielsen S (December 2016). "Aquaporins in the Spinal Cord". International Journal of Molecular Sciences. 17 (12): 2050. doi:10.3390/ijms17122050. PMC 5187850 . PMID 27941618.

[Saadoun_2010-6] Saadoun S, Papadopoulos MC (July 2010). "Aquaporin-4 in brain and spinal cord oedema". Neuroscience. 168 (4): 1036–46. doi:10.1016/j.neuroscience.2009.08.019. PMID 19682555.

[Gleiser_2016-7] Gleiser C, Wagner A, Fallier-Becker P, Wolburg H, Hirt B, Mack AF (August 2016). "Aquaporin-4 in Astroglial Cells in the CNS and Supporting Cells of Sensory Organs-A Comparative Perspective". International Journal of Molecular Sciences. 17 (9): 1411. doi:10.3390/ijms17091411. PMC 5037691 . PMID 27571065.

[Verkman_2013-8] Verkman AS, Phuan PW, Asavapanumas N, Tradtrantip L (November 2013). "Biology of AQP4 and anti-AQP4 antibody: therapeutic implications for NMO". Brain Pathology. 23 (6): 684–95. doi:10.1111/bpa.12085. PMC 3890327 . PMID 24118484.

[Chu_2016-9] Chu H, Huang C, Ding H, Dong J, Gao Z, Yang X, Tang Y, Dong Q (August 2016). "Aquaporin-4 and Cerebrovascular Diseases". International Journal of Molecular Sciences. 17 (8): 1249. doi:10.3390/ijms17081249. PMC 5000647 . PMID 27529222.

[Hubbard_2017-10] Hubbard JA, Szu JI, Binder DK (March 2017). "The role of aquaporin-4 in synaptic plasticity, memory and disease". Brain Research Bulletin. 17: 118–129. doi:10.1016/j.brainresbull.2017.02.011. PMID 28274814.

[:0-11] Desai, Bhargav; Hsu, Ying; Schneller, Benjamin; Hobbs, Johnathan G.; Mehta, Ankit I.; Linninger, Andreas (Summer 2016). "Hydrocephalus: the role of cerebral aquaporin-4 channels and computational modeling considerations of cerebrospinal fluid". Neurological Focus. 41 (3): 1–17. doi:10.3171/2016.7.FOCUS16191. PMID 27581320.

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