Njengoba nje abahleli basemadolobheni behlela ngokucophelela ukuhamba kwezimoto ezindaweni ezisemadolobheni, amaseli alawula ngokucophelela ukunyakaza kwama-molecule ngaphesheya kwemingcele yawo yenuzi. Esebenza njengabalindi abancane kakhulu, ama-nuclear pore complexes (ama-NPC) afakwe kulwelwesi lwenuzi agcina ukulawula okunembile kulo mkhakha wama-molecule. Umsebenzi omangalisayo ovela eTexas A&M Health wembula ukukhetha okuyinkimbinkimbi kwalolu hlelo, okungenzeka kunikeze imibono emisha ngezifo ze-neurodegenerative kanye nokuthuthukiswa komdlavuza.
Ukulandelela Okuguquguqukayo Kwezindlela Zama-Molecular
Ithimba locwaningo likaDkt. Siegfried Musser eTexas A&M College of Medicine lihole ucwaningo mayelana nokuthutha okusheshayo, okungenazingxabano kwama-molecule ngokusebenzisa isithiyo se-nucleus esine-membrane ephindwe kabili. Incwadi yabo ephawulekayo ye-Nature ichaza okutholakele okuguqukayo okwenziwe kwaba nokwenzeka ubuchwepheshe be-MINFLUX - indlela ethuthukisiwe yokuthwebula izithombe ekwazi ukubamba ukunyakaza kwama-molecule e-3D okwenzeka ngama-millisecond ngezikali cishe ngokuphindwe kayi-100,000 kunobubanzi bezinwele zomuntu. Ngokuphambene nokucabanga kwangaphambilini mayelana nezindlela ezihlukanisiwe, ucwaningo lwabo lubonisa ukuthi izinqubo zokungenisa nokuthumela izinto zenuzi zabelana ngemizila ehambisanayo ngaphakathi kwesakhiwo se-NPC.
Inselele Yokuthola Okumangalisayo Yamamodeli Akhona
Okubonwe yithimba kwembule amaphethini omgwaqo angalindelekile: ama-molecule ahamba ngezindlela ezimbili ngokusebenzisa iziteshi ezincishisiwe, ezulazula komunye nomunye kunokulandela imizila ezinikele. Okuphawulekayo ukuthi lezi zinhlayiya zigxila eduze kwezindonga zeziteshi, zishiya indawo ephakathi ingenalutho, kuyilapho intuthuko yazo yehla kakhulu - cishe izikhathi eziyi-1,000 kancane kunokunyakaza okungavinjelwe - ngenxa yamanethiwekhi amaprotheni avimbayo adala indawo ene-syrup.
UMusser uchaza lokhu “njengesimo sethrafikhi esiyinselele kakhulu ongasicabanga – ukuhamba ngezindlela ezimbili ngokusebenzisa izindlela ezincane.” Uyavuma, “Okutholakele kwethu kuveza inhlanganisela engalindelekile yamathuba, kwembula ubunzima obukhulu kunalokho okwakusikiselwa yimicabango yethu yokuqala.”
Ukusebenza Kahle Naphezu Kwezithiyo
Ngokuthakazelisayo, izinhlelo zokuhamba ze-NPC zibonisa ukusebenza kahle okumangalisayo naphezu kwalezi zithiyo. UMusser uqagela, “Ubuningi bemvelo be-NPC bungavimbela ukusebenza ngokweqile, kunciphise ngempumelelo ukuphazamiseka kokuncintisana kanye nezingozi zokuvinjelwa.” Lesi sici sokuklama esingokwemvelo sibonakala sivimbela ukukhiya kwama-molecule, Lapha'inguqulo ebhalwe kabusha ene-syntax ehlukahlukene, isakhiwo, kanye nokuhlukana kwezigaba ngenkathi kulondolozwa incazelo yokuqala:
Ithrafikhi Yamamolekyuli Ithatha Indlela Ehlukile: Ama-NPC Embula Izindlela Ezifihliwe
Esikhundleni sokuhamba ngqo nge-NPC'Ku-axis ephakathi, ama-molecule abonakala ehamba ngesinye seziteshi zokuthutha ezikhethekile eziyisishiyagalombili, ngasinye siboshwe esakhiweni esinjengesipikha eduze kwembobo.'indandatho yangaphandle. Lokhu kuhlelwa kwendawo kusikisela indlela yokwakha eyisisekelo esiza ekulawuleni ukugeleza kwama-molecule.
UMusser uyachaza,"Nakuba i-yeast nuclear pores zaziwa ukuthi ziqukethe'ipulaki eliphakathi,'Ukwakheka kwayo okunembile kusalokhu kuyimfihlakalo. Emangqamuzaneni omuntu, lesi sici sinayo'Akukabonwa, kodwa ukuhlukaniswa okusebenzayo kungenzeka—kanye nembobo'isikhungo singasebenza njengendlela eyinhloko yokuthumela i-mRNA."
Ukuxhumana Kwezifo Nezinselele Zokwelapha
Ukungasebenzi kahle kwe-NPC—isango elibalulekile lamaselula—kuye kwahlotshaniswa nezinkinga ezinkulu zezinzwa, okuhlanganisa ne-ALS (Lou Gehrig).'isifo se-Alzheimer),'s, kanye noHuntington'isifo sika-s. Ngaphezu kwalokho, ukwanda komsebenzi wokushushumbisa i-NPC kuhlotshaniswa nokuqhubeka komdlavuza. Nakuba ukuqondisa izindawo ezithile ze-pore kungasiza ngokombono ukuvala ukuvinjelwa noma ukwehlisa ukuthutha ngokweqile, uMusser uxwayisa ngokuthi ukuphazanyiswa komsebenzi we-NPC kuthwala izingozi, njengoba kunendima ebalulekile ekusindeni kwamaseli.
"Kumelwe sihlukanise phakathi kwamaphutha ahlobene nezokuthutha kanye nezinkinga ezihlobene ne-NPC'ukuhlanganiswa noma ukuhlukaniswa,"uyaphawula."Nakuba ukuxhumana okuningi kwezifo kungenzeka kuwele esigabeni sokugcina, kukhona okuhlukile—njengokuguqulwa kwezakhi zofuzo ze-c9orf72 ku-ALS, okudala ama-aggregates avimba imbobo ngokomzimba."
Iziqondiso Zesikhathi Esizayo: Ukumaka Imizila Yezimpahla kanye Nokuthwebula Izithombe Zamaseli Aphilayo
UMusser kanye nomlingani wakhe uDkt. Abhishek Sau, waseTexas A&M'I-Joint Microscopy Lab, ihlela ukuphenya ukuthi ngabe izinhlobo ezahlukene zempahla—njenge-ribosomal subunits kanye ne-mRNA—balandela izindlela ezihlukile noma bahlangane emizileni ehlanganyelwe. Umsebenzi wabo oqhubekayo nabalingani baseJalimane (i-EMBL kanye ne-Abberior Instruments) ungase futhi uvumelanise i-MINFLUX ukuze kuthathwe izithombe ngesikhathi sangempela emaseli aphilayo, okunikeza imibono engakaze ibonwe yezinguquko zokuhamba kwenuzi.
Lolu cwaningo lusekelwa uxhaso lwe-NIH, lushintsha ukuqonda kwethu ngezinhlelo zokusebenza zamaselula, lubonisa indlela ama-NPC agcina ngayo ukuhleleka edolobheni elikhulu elimatasa le-nucleus.
Isikhathi sokuthunyelwe: Mashi-25-2025
