GJB6
Međuprostorni vezni protein beta-6 (GJB6), znan i kao koneksin 30 (Cx30) — je protein koji je kod ljudi kodiran genom GJB6.[5][6][7] Koneksin 30 (Cx30) je jedan od nekoliko spojnih proteina za uspostavljenje međućelijskih veza koji se eksprimira u unutrašnjem uhu.[8] Utvrđeno je da mutacije u genima za ove veze dovode i do sindromske i do nesindromske gluhoće.[9] Mutacije u ovom genu povezane su s Cloustonovim sindromom (tj. hidrotskom ektodermnom displazijom).
GJB6 | |||||||||||||||||||||||||
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Aliasi | GJB6 | ||||||||||||||||||||||||
Vanjski ID-jevi | OMIM: 604418 MGI: 107588 HomoloGene: 4936 GeneCards: GJB6 | ||||||||||||||||||||||||
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Ortolozi | |||||||||||||||||||||||||
Vrste | Čovjek | Miš | |||||||||||||||||||||||
Entrez | |||||||||||||||||||||||||
Ensembl | |||||||||||||||||||||||||
UniProt | |||||||||||||||||||||||||
RefSeq (mRNK) |
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RefSeq (bjelančevina) |
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Lokacija (UCSC) | Chr 13: 20.22 – 20.23 Mb | Chr 14: 57.36 – 57.37 Mb | |||||||||||||||||||||||
PubMed pretraga | [3] | [4] | |||||||||||||||||||||||
Wikipodaci | |||||||||||||||||||||||||
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Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 261 aminokiselina, a molekulska težina — 30.387 Da.[10]
10 | 20 | 30 | 40 | 50 | ||||
---|---|---|---|---|---|---|---|---|
MDWGTLHTFI | GGVNKHSTSI | GKVWITVIFI | FRVMILVVAA | QEVWGDEQED | ||||
FVCNTLQPGC | KNVCYDHFFP | VSHIRLWALQ | LIFVSTPALL | VAMHVAYYRH | ||||
ETTRKFRRGE | KRNDFKDIED | IKKQKVRIEG | SLWWTYTSSI | FFRIIFEAAF | ||||
MYVFYFLYNG | YHLPWVLKCG | IDPCPNLVDC | FISRPTEKTV | FTIFMISASV | ||||
ICMLLNVAEL | CYLLLKVCFR | RSKRAQTQKN | HPNHALKESK | QNEMNELISD | ||||
SGQNAITGFP | S |
- Simboli
Funkcija
urediPorodica koneksinskih gena kodira proteinske podjedinice kanala koji spajaju pukotinske međućelijske veze i posreduju u direktnoj difuziji iona i metabolita između citoplazmi susjednih ćelija. Koneksini obuhvataju plazmamembranu četiri puta (vidi sliku), a amino– i karboksi-terminalne regije okrenute su prema citoplazmi. Koneksinski geni eksprimiraju se na specifičan način za ćelijski tip sa preklapajućom specifičnošću. Spojni kanali s razmakom imaju jedinstvena svojstva, ovisno o tipu koneksina koji čine kanal (prema OMIM-u).[7]
Koneksin 30 je rasprostranjen u dva različita sistema spajanja razmaka, koji se nalaze u pužnicama: mreža spoja epitelnih pukotinskih međućelijskih veza koja spaja nesenzorne epitelne ćelije i mreža uskih spojevaa u vezivno tkivo, koja spaja ćelije vezivnog tkiva. Uske veze služe važnoj svrsi recikliranja kalijevih iona koji prolaze kroz trepljaste ćelije tokom mehanotransdukcije nazad u endolimfu.[11]
Koneksin 30 je kolokaliziran s koneksinom 26.[12] Utvrđeno je da Cx30 i Cx26 tvore heteromerne i heterotipske kanale. Biohemijska svojstva i propusnost ovih složenijih kanala razlikuju se od homotipskih kanala Cx30 ili Cx26.[13] Prekomjerna ekspresija Cx30 u null miševima Cx30 obnovila je ekspresiju Cx26, funkcioniranje kanala normalnog razmaka i signalizaciju kalcija, ali je u nul miševa Cx30 ekspresija Cx26 promijenjena. Pretpostavlja se da koregulacija Cx26 i Cx30 ovisi o signalizaciji fosfolipaze C i NF-κB putu.[14]
Pužnica sadrži dva tipa ćelija, slušne trepljaste ćelije za mehanotransdukciju i potporne ćelije. Kanali međuprostornog spajanja nalaze se samo između ćelija koje podržavaju pužnicu.[15] Dok su pukotinske međućelijske veze u unutrašnjem uhu kritično uključene u recikliranje kalija u endolimfi, ekspresija koneksina u potpornim ćelijamama koje okružuju Cortijev organ podupire oporavak lezija epitelnog tkiva nakon gubitka čulnih treplastih ćelija. Eksperiment sa nul miševima Cx30 otkrio je nedostatke u zatvaranju lezija i popravku Cortijevog organa nakon gubitka trepljastih ćelija, što ukazuje da Cx30 ima ulogu u regulaciji odgovora na popravak lezija.[16]
Klinički značaj
urediSlušni
urediKoneksin 26 i koneksin 30 općenito su prihvaćeni kao proteini spojeva koji prevladavaju u pužnicama. Eksperimenti s genetičkim nokaut-miševima pokazali su da nokaut ili Cx26 ili Cx30 proizvodi gluhoću.[17][18] Međutim, novija istraživanja sugeriraju da nokaut Cx30 proizvodi gluhoću zbog kasnije regulacije Cx26, a jedno je istraživanje na mišu pokazalo da je mutacija Cx30 koja čuva polovinu ekspresije Cx26 pronađena u normalnih miševa Cx30 rezultirala nesmetanim sluhom.[19] Smanjena ozbiljnost nokauta Cx30 u usporedbi s nokautom Cx26 potkrijepljena je studijom koja je ispitivala vremenski tok i obrasce degeneracije trepljastih ćelija u pužnici. Nx miševi Cx26 pokazali su bržu i raširenu ćelijsku smrt od nultih miševa Cx30. Postotak gubitka trepljastih ćelija bio je manje rasprostranjen i učestao u pužnici null miševa Cx30.[20]
Reference
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Vanjski linkovi
uredi