I-Cutting-Edge Imaging Ivula Izimfihlo Ze-Nuclear Pore Molecular Traffic Control

Njengabahleli basemadolobheni abahlela ngokucophelela ukuhamba kwezimoto enkabeni yedolobha, amaseli alawula ngokucophelela ukunyakaza kwamangqamuzana emingceleni yawo yenuzi. Isebenza njengabalindisango abancane kakhulu, ama-nuclear pore complexes (NPCs) ashumekwe kulwelwesi lwenuzi agcina ukulawula okunembile kulokhu kuhweba kwamangqamuzana. Umsebenzi odabukisayo ovela e-Texas A&M Health wembula ukukhetha okuyinkimbinkimbi kwalolu hlelo, okungenzeka kunikeze imibono emisha ngezinkinga ze-neurodeergenerative kanye nokuthuthukiswa komdlavuza.

Ukulandelela kwe-Revolutionary ye-Molecular Pathways

Ithimba locwaningo likaDkt. Siegfried Musser e-Texas A&M College of Medicine lisungule uphenyo lokuhamba ngokushesha, okungashayisani kwama-molecule ngokusebenzisa umgoqo we-nucleus one-double-membrane. Ushicilelo lwabo oluyingqopha-mlando lweMvelo lunikeza imininingwane ngemiphumela yoguquko eyenziwe yaba nokwenzeka ngobuchwepheshe be-MINFLUX - indlela ethuthukisiwe yokuthwebula ekwazi ukuthwebula ukunyakaza kwamangqamuzana e-3D okwenzeka ngama-millisecond esikalini cishe izikhathi eziyi-100,000 kahle kunobubanzi bezinwele zomuntu. Ngokuphambene nokucatshangelwa kwangaphambili mayelana nezindlela ezihlukanisiwe, ucwaningo lwabo lubonisa ukuthi izinqubo zokungenisa nokuthunyelwa kwezikhali zenuzi zabelana ngemizila egqagqene ngaphakathi kwesakhiwo se-NPC.

Okutholakele Okumangazayo Kunselele Amamodeli Akhona

Okuphawulwe yiqembu kwembule amaphethini ethrafikhi angalindelekile: ama-molecule azulazula ezinhlangothini zombili eziteshini eziminyene, azulazula kunokulandela imizila ezinikele. Ngokuphawulekayo, lezi zinhlayiya zigxila eduze kwezindonga zesiteshi, zishiya indawo emaphakathi ingenamuntu, kuyilapho ukuqhubeka kwazo kuhamba kancane kakhulu - cishe izikhathi ezingu-1,000 ezihamba kancane kunokunyakaza okungavinjelwe - ngenxa yamanethiwekhi amaprotheni avimbelayo adala indawo emanzi.

U-Musser uchaza lokhu “njengesimo sethrafikhi esiyinselele kakhulu ongakucabanga - ukugeleza kwezindlela ezimbili eziphasejini eziwumngcingo.” Uyavuma, “Esikutholile kunikeza inhlanganisela yamathuba angalindelekile, eveza inkimbinkimbi enkulu kunemibono yethu yasekuqaleni eyayisikiselwe.”

Ukusebenza Ngempumelelo Naphezu Kwezithiyo

Ngokumangalisayo, izinhlelo zokuthutha ze-NPC zikhombisa ukusebenza kahle okumangalisayo naphezu kwalezi zingqinamba. UMusser uyaqagela, "Ubuningi bemvelo be-NPC bungase buvimbele ukusebenza komthamo oweqile, kunciphise ngempumelelo ukuphazamiseka kokuncintisana kanye nezingozi zokuvinjwa." Lesi sici somklamo ongokwemvelo sibonakala sivimbela i-gridlock yamangqamuzana, Lapha'ngithole inguqulo ebhalwe kabusha ene-syntax ehlukahlukene, ukwakheka, nokuhlukana kwezigaba kuyilapho ilondoloza incazelo yasekuqaleni:

I-Molecular Traffic Ithatha Indlela: Ama-NPC Aveza Izindlela Ezifihliwe

Esikhundleni sokuhamba uqonde ku-NPC'ku-axis emaphakathi, ama-molecule abonakala ezulazula kwelinye lamashaneli ayisishiyagalombili akhethekile okuthutha, ngalinye livalelwe esakhiweni esikhulumayo eduze kwembotshana.'s indandatho yangaphandle. Lolu hlelo lwendawo luphakamisa indlela yezakhiwo eyisisekelo esiza ukulawula ukugeleza kwamangqamuzana.

UMusser uyachaza,“Ngenkathi izimbotshana zemvubelo zenuzi zaziwa ukuthi ziqukethe a'ipulaki ephakathi,'ukwakheka kwayo okuqondile kuseyimpicabadala. Kumaseli omuntu, lesi sici asizange't kubhekwe, kodwa ukuhlukaniswa okusebenzayo kuyabonakala-kanye nembotshana's isikhungo singasebenza njengomzila oyinhloko wokuthekelisa we-mRNA.”

Ukuxhumana Kwezifo Nezinselele Zokwelapha

Ukungasebenzi ku-NPC-isango elibalulekile lamaselula-uboshelwe ezinkingeni ezinzima zemizwa, okuhlanganisa ne-ALS (Lou Gehrig's isifo), i-Alzheimer's, kanye noHuntington's isifo. Ukwengeza, ukwanda komsebenzi wokushushumbiswa kwe-NPC kuxhumene nokuqhubeka komdlavuza. Nakuba ukukhomba izifunda ezimbotshana ezithile ezimbotshana kungasiza ngokwethiyori ukuthi kuvuleke ukuvinjwa noma kubambezele izinto zokuhamba ngokweqile, u-Musser uxwayisa ngokuthi ukuphazamisa ukusebenza kwe-NPC kunezingozi, uma kubhekwa indima yakhona ebalulekile ekusindeni kweseli.

“Kufanele sehlukanise phakathi kwamaphutha ahlobene nezokuthutha kanye nezindaba ezixhumene ne-NPC'ukuhlanganisa noma ukuqaqa,”uyaphawula.“Nakuba izifo eziningi ezixhumene nazo ziwela esigabeni sokugcina, kukhona okuhlukile-njengokuguqulwa kofuzo kwe-c9orf72 ku-ALS, okudala izilinganiso ezithikameza imbobo.”

Izikhombisi-ndlela zesikhathi esizayo: Ukwenza Imephu Yemizila Yezimpahla kanye Nezithombe Zeseli Elibukhoma

U-Musser kanye nomhleli uDkt. Abhishek Sau, wase-Texas A&M's I-Joint Microscopy Lab, ihlela ukuphenya ukuthi ngabe izinhlobo ezahlukene zempahla-njengama-ribosomal subunits kanye ne-mRNA-landela izindlela ezihlukile noma uhlangane emizileni eyabiwe. Umsebenzi wabo oqhubekayo nozakwethu baseJalimane (EMBL kanye ne-Abberior Instruments) ungase futhi uvumelanise i-MINFLUX ukuze uthole izithombe zesikhathi sangempela kumaseli aphilayo, unikeze imibono engakaze ibonwe yokuguquguquka kwezokuthutha zenuzi.

Lusekelwa uxhaso lwe-NIH, lolu cwaningo lulolonga kabusha ukuqonda kwethu ukuhanjiswa kweselula, lubonisa indlela ama-NPC agcina ngayo ukuhleleka edolobheni elikhulu elimatasa lenucleus.