
chumbanam-oottam samyojanam

vesicle thurakkukayum adaykkukayum cheiyunna oru tharam synaptic vesicle releasaanu chumbanam-oodikkal fusion. eee tharatthilulla exocytosisiloode, vesicle doock cheyyukayum presignaptic membranil kshanikamaayi fuse cheyyukayum sinaapsiludaneelam athinte neuro traansmittarukal purathuvidukayum athinusesham vesicle veendum upayogikkukayum cheiyunnu.
chumbanam-oottam poornna samyojanathil ninnu vyathyasthamaan, avide vesicle poornnamaayum plasma membranilekku thakarukayum pinneedu clathrin-kottu-ashrita prakriyayiloode veendedukkukayum cheiyunnu. synaptic vesikkilukal pree synaptic membranumaayi samyojippichu neuro traansmittar "kwanda" yill purathuvidaamenna ashayam 1955 ll bernard kaatsum jose dell kaasttilloyum aadyamaayi avatharippichu, naadi terminalukalude aadya em chithrangal aadyamaayi prathyakshappettu. electron microscopyl shakthamayi uthejippicha thavalayude neuro muscular jangshanukal parishodhicha sesham 1973 ll bruno secarelli, electrophysiology, electron microscopy, drutha freesing teknikkukal enniva upayogichu addehathinte grouppinte pravarthanangalaal parokshamaayi pinthunaykkukayum cheythu. oresamayam membran kappaasittans, amparometric traansmittar release alavukal ennivayekkurichulla aadya padanangal nadathiyathinu sesham sekkarelliyude sahakaarikalaan yadhaartha padam, chumbanam-oodikkal, avatharippichathu, koodaathe traansiyant vesicle fusion samayat srava uthppannangal yadhaarthathil purathuvidaamennu soochippichu.
innu, phul fusion, kiss-aandu-rann fusion ennivayekkurichum synaptic releasinu pinnile samvidaanangalekkurichu kooduthal krithyamaaya chithram chithreekarikkunna model eathaanu ennathinekkurichum munnottum pinnotum charchakal nadakkunnundu. electron micrographukalil nireekshikkappedunna sravathethudarnnu bhaagikamaayi shoonyamaaya srava vesikkilukalude vardhicha shekharanamaanu chumbanam-oottam modalinu anukoolamaaya ettavum sakthamaaya thelivukal. sravathethudarnnu bhaagikamaayi shoonyamaaya vesikkilukal adinjukoodunnathu soochippikkunnathu srava prakriyayil, vesicular ulladakkathinte oru bhaagathinu maathrame koshatthil ninnu purathukadakkaan kazhiyoo, srava vesikkilukal kosha plasma membranumaayi thaalkkaalikamaayi thudarcha sthaapikkukayum avayude ulladakkathinte oru bhagam puranthallukayum thudarnnu verpeduthi veendum seal cheyyukayum cheythaal maathrame ithu saadhyamaakoo.
kandethal.
1955ll kaatsum dell kaasttilloyum chernnaanu traansiyant vesicle fusion sidhaantham eduthathu. ennirunnaalum, aadyathe chittayaya padanangal nadathiyathu secarelliyum mattullavarum aanu. 1973ll secarelli thudangiyavar. thavalayude neuro muscular jangshanukal padikkukayum endocytosed oorganellukal thirichariyaan hozhsaradish peroxidase polulla markerukal upayogichu avaye uthejippikkukayum 20 minitt muthal 4 manikkoor vareyulla kaalayalavil neriya uthejanam (2 hearts) allengil sakthamaaya uthejanam (10 hearts) protocolukal upayogikkukayum cheythu. 4 manikkoor kuranja uthejanathil, secarelli thudangiyavar. kaalakramena hozhsaradish peroxidase label cheytha vesikkilukalil vardhanayundaayathaayum valia oorganellukalil vardhanavu illennum kandethi, ithu vesikkilukal presignaptic membranumaayi vegathil samyojippikkunnathum neuro traansmittarukal purathuvannathinushesham athil ninnu verpiriyunnathum soochippikkunnu. uthejanathinte kuranja aavruthikalil, uthejanathinte samayathum sheshavum mikka vesikkilukalum pree synaptic membrainil ninnu vegathil punarnirmmikkappedunnu avar anumaanichu. sekkarelliyude laabile kooduthal padanangal electrophysiological, morphological dattakal thaarathamyam cheythukondu shanikamaaya samyojanathinte sidhaanthathekkurichulla thelivukal shekharichu. prathyekichum, freeze cheytha-fracture cheytha presignaptic membranukalilum terminalukalil ninnu labhicha electron-microscope chithrangalilum naadiyilekku orotta shock nalkiyathinu sesham kurachu ems vegathil freeze cheytha vesicle fusionukalude chithrangal parishodhichu. 1993-ll alvares dii toledo sahapravarthakarum oru shanikamaaya fusing vesicle thalkshanamaayi thurakkumbol srava uthppanna release undaakunnath nerittu pradharshippichu, membran kappaasittansinte alavu (uparithala vistheernnathile mattangal nireekshikkunna) amparometric kandethalumayi samyojippichu. ithu fessineyum mattullavareyum nayichu. shanikamaaya samyojanathinu anukoolamaaya ellah paroksha thelivukalum aavarthikkukayum chumbanam-oottam enna padam nalkukayum cheyyuka. kosha plasma membranile sthiramaaya kapp aakruthiyilulla lipoprotein gadanayaaya porosome kandethiyathil ninnaan shanikamaaya allengil chumbanam-oottam fusionullah ettavum sradheyamaaya thelivukal labhichathu, avide srava vesikal kshanikamaayi doock cheyyukayum koshatthil ninnu intra-vesicular ulladakkangal purathuvidunnathinu fuse cheyyukayum cheiyunnu.
chumbanam nadathukayum oodukayum cheiyunnathinte thelivukal.
secarelliyum mattullavarum chernnu chumbanam nadathaanulla samvidaanam kandethiyathode.thudarnnulla niravadhi padanangal chumbanam-oottam samyojanathe pinthunaykkunna thelivukal nalkunnu. ellah padanangalum soochippikkunnathu poornna fusionekkaal chumbanam-oottam-fusion rund pradhana gunangalundennaanu 1) chumbanam-oottam kooduthal kaaryakshamamaya vesicle recycling prapthamaakkunnu, 2) chumbanam-oottam-oru cheria fusion susiravum neuro traansmittarukal yadhaarthathil purathuvidunna churungiya samayavum kaaranam neuro traansmittar ethratholam purathuvarunnu ennathu parimithappedutthaan kazhiyum. chumbanam-oottam thelivukalude pradhana prashnangalilonn, thudarnnu chumbanam-oottam ennivaykkethiraaya niravadhi ethir vaadangalkku adisthaanam, fusion valare cheruthaanu ennathinaal, oru yadhaartha chumbanam-oottam ivant pidichedukkaan valare budhimuttaanu. ennirunnaalum, sravathethudarnnu bhaagikamaayi shoonyamaaya vesikkilukal adinjukoodunnathu chumbanam nadathunnathinulla samvidaanathe shakthamayi anukoolikkunnu, ithu soochippikkunnathu srava prakriyayil, vesicular ulladakkathinte oru bhaagathinu maathrame koshatthil ninnu purathukadakkaan kazhiyoo, sravikkunna vesikkilukal kosha plasma membranumaayi thaalkkaalikamaayi thudarcha sthaapikkukayum avayude ulladakkathinte oru bhagam puranthallukayum thudarnnu verpeduthi veendum seal cheyyukayum cheythaal maathrame ithu saadhyamaakoo. srava vesicle valuppathinte oru bhagam maathram alakkunna kosha plasma membranile sthiramaaya gadanakalaanu porosomukal ennathinaal, srava vesikkilukal "kshanikamaayi" doock cheyyukayum poornnamaaya thakarchaykku pakaram thudarcha sthaapikkukayum cheiyunnuvennu theliyikkunnu.
elikalude pancreatic beetta cellukal.
elii pancreatic beetta cellukal chumbanam-oottam samyojanathiloode neuro traansmittarukal purathuvidunnu. endocrine, neuroendocrine koshangalil, synaptic polulla vesikkilukal (slv) chumbikkukayum oodukayum cheiyunnu, ennaal valia dense coor vesikkilukal (eldcv) chumbikkukayum oodukayum cheiyunnundo ennathu vivaadamaanu. ell. dii. sii. vikal chumbanam-oottam exocytosisinu vidheyamaakunnathaayi padanangal theliyichittundu. mcdonald thudangiyavar. elikalude beetta koshangalil chumbanam nadathukayum pravarthippikkukayum cheiyunna exocytosis parisodhikkaan onniladhikam sameepanagal upayogichu. 10 emm glucosinteyum 5 emm forscollin, mcdonald muthalaayavayudeyum saannidhyathil kedukoodaattha elii beetta koshangalude membran paachukal nireekshikkunnathiloode. chila vesikkilukal chumbikkukayum oodukayum cheythathayi kandethi, oru exocytotic sambhavavum thudarnnu samanamaaya alavilulla endocytotic sambhavavum kaanunnu. ell. dii. sii. vii exocytosisinte 25 sathamaanavum ezz. ell. vii exocytosisinte 28 sathamaanavum chumbanam nadathukayum oodukayum cheiyunna sambhavangalaanu. ell. dii. sii. vii. chumbanam-oottam 25 sathamaanam forscollinte saannidhyathil nadannappol, forscollinte abhaavathil ell. dii. sii. vii. chumbanam-oottam samyojanam 7 sathamaanam samayam maathramaan sambhavichathu. forscollin cyclic aambu (camp) alavu uyarthunnathinaal, elii pancreatic beetta cellukalile ell. dii. sii. vii. chumbanam-rann fusionile samvidaanathil camp valare pradhana punk vahikkunnu.
chumbanasamayathu ell. vii. vii (sushira vyaasam 0.8 +/- 0.1 enn. emm), ell. dii. sii. vii (sushira vyaasam 1.4 +/- 0.1 enn. emm) fusion sushirangal gaama-aminobutoric assid (gaba), adenosine triphosphate (eiii. tii. pii) ennivayude puranthallal anuvadikkunnathra valuthaanennu theliyikkappettittund, pakshe elikalude pancreatic beetta cellukalil insulin purathuvidunnathinu valare cheruthaanu. athinaal, insulin ulppedunna medical sankeernathakalil chumbanam nadathukayum oodukayum cheiyunna samvidaanam ulppedaam.
hippocampal synapsus.
hippocampasil sthithicheyyunna neuronukalude sinaapsukalil chumbanam-aandu-rann exocytosis sambhavikkunnathayi theliyikkappettittund. efm 1-43, oru markeraayi vesikkilukalilo membranilo cherttha oru amphiphile dye, hippocampal sinaapsukalile chumbanatheyum oottatheyum pinthunaykkunnathil nirnaayaka punk vahikkunnu. hippocampal sinaapsukalil, efm 1-43 dye vesiclil praveshikkaano rakshappedaano anuvadikkaathe thalachorile oru eksaittettari neuro traansmittaya glutamettinte saadhaarana release vesikkilukal anuvadikkunnuvennu theliyikkappettittund, ithu chumbanam-oottam soochippikkunna oru shanikamaaya samvidaanathe soochippikkunnu. ausmolaarittiyile vardhanavu hippocampal sinaapsukalil chayam kuranjathaayi kaanikkunnu. vyathyastha hypertonic laayanikalil, 1.5 oasmil uthejippicha vesikalil ninnu purathuvarunnathinekkaal 0.50 oasmil uthejippicha vesikalil ninnu 70 sathamaanam kooduthal efm 1-43 chayam puratthuvannu. athinaal shareerathinte hypertonic pradeshangalil sthithi cheiyunna vesikkilukal exocytosisinte chumbanam-oottam modinu vidheyamaakaanulla saadhyatha kooduthalaanu.
mitocondria.
aantharika membran metteeriyalukal kaimarunnathil mitocondria chumbanam-rann fusion pradarshippikkunnu. mitocondrial matricks-targettucheytha green-foto activated, redu-fluorescent keey. eph. pii, sian-foto activated, green-fluorescence pagg. eph. pii enniva upayogichulla padanangal elikalude koshangalile keey. eph. pii, pagg. eph. pii enniva oru mitocondriyanil ninnu mattoru mitocondrianilekku traansiyant fusioniloode kaimaattam cheyyappettathayi kaanikkunnu, ithu oru chumbanam-rann samvidaanam soochippikkunnu. orotta oorganellinu kaaranamaaya mitocondriyayude poornna samyojanathil ninnu vyathyasthamayi, rund mitocondriyayude shanikamaaya chumbanam-oonn-rann samyojanam rund vyathyastha stharangalkk kaaranamaayi.
opttik atrophy 1 (opaa 1) jeeninte krithrimathvam mitocondria thammilulla samyojanathil rasakaramaaya phalangal srishtichu. opaa 1 jeenine nishabdamaakkunnathu 24 manikkoorinusesham mitocondriyayude poornna fusion pravartthanam kuraykkukayum opaa 1 jeane 48 manikkoor nishabdamaakkiya sesham poornna fusion pravartthanam poornnamaayum illaathaakkukayum cheythu. opaa 1 nishabdathayude 24 manikkoorinusesham shanikamaaya chumbanam-oottam fusion pravartthanam athepadi thudarnnu. kuranja alavilulla opaa 1 jeane expression uyarnna alavilulla opaa 1 jeane expression ulla chumbanavum oottavum thammilulla samyojanam ettavum saadhaaranamaanu. thalphalamaayi, chumbanam-oottam ennivayumaayi bandhappett mitocondriyayile samyojanathe opaa 1 expression niyanthrikkunnu.
mitocondriyayile chumbanam-oottam samyojanam poornna samyojanavumaayi thaarathamyappeduthumbol kuranja samayathekku mitocondriyaye chalanaseshi kuranja avasthayil nilanirthaan sahayikkunnu. liu thudangiyavar. chumbanam-oottam, poornna samyojanam ennivayum mitocondrial chalanakshamathayil avayude phalangalum pareekshichu, rund tharatthilulla samyojanavum thudakkathil mitocondrial chalanathmakatha kurayaan kaaranamaayengilum chumbanam-oottam samyojanam punasthaapikkappedukayum chumbanam-oottam ivant avasaanichathinu thottupinnaale mitocondrial chalanathmakatha vardhippikkukayum cheythathayi kandethi. poornnamaaya samyojanathekkaal mitocondrial bio energetics niyanthrikkunnathinulla mikacha samvidaanam chumbanam-oottam samyojanam nalkunnu.
niyanthranam.
kaalsyam ashrita aaktin coating.
vesikkilukalude aaktin coating vazhi chumbanam-oottam fusion sthirappeduthumennu karuthappedunnu. fm 1-43-nte vesicle ettedukkunnathinulla parisodhana, vesikkilukal membranumaayi samyojippikkappettpol, chumbanam-oottam samvidaanathinu aaktin coating oru aavashyamaaya ghattamaanenn gaveshakarkk shradhikkaan anuvadichu. presinaptic membranumaayi samyojippichu sekkantukalkk sesham beetaa-aaktin-green fluorescent protein (jii. eph. pii) fluoresed cheytha vesikkilukal (eph. emm. <aii. dii. 1> upp take kaanikkunnath pole), ennaal fuse cheyyaatha vesikkilukal orikkalum fluoresed cheiyunnilla, ithu chumbikkunnathinum oodunnathinum oru aaktin coating aavasyamaanennu soochippikkunnu. aaktin monomerukalude polymerisationil ninnaan eee aaktin coating vannath.
shanikamaaya chumbanam-oottam samyojanathinu aavashyamaaya aaktin coating prakriyaykku kaalsyam madhyasthatha vahikkunnu. vesikkilukalude aaktin coating bappatta-aam vazhi thadanju, ithu kaalsyam neekkam cheiyunnu. bapta-aam upayogathiloode kaalsyatthinte abhaavathil, ellah fuse cheytha vesikkilukalum pree synaptic membranumaayi bandhippichirikkukayum ennaal athinte neuro traansmittarukal purathuvidathirikkukayum cheythu, ithu aaktin coating nirmmikkaan kaalsyam aavasyamaanennum vesicle unloading allengil vesicle release cheiyunnathinulla samvidaanathil aaktin coating utharavaadiyaanennum soochippikkunnu.
myosin II.
myosin II aanu chumbanam-oottam exocytosis niyanthrikkunnath. neuroendocrine pisi12 koshangalile total intenal reflection fluorescence microscopy (trfm) upayogichulla padanangal kaanikkunnath myosin II chumbanam-aandu-rann exocytosis samayat fusion pore dynamics niyanthrikkunnu ennaanu. emrfp (monomeric redu fluorescent protein) tagg cheytha tissuevilum veenas tagg cheytha braine tissuevilum saadhaarana myosin II regulatory laitt cheyin (rlc) amithamaayi prakadippikkunnathu deerghakaala release kainattiksin kaaranamaayi, athesamayam myosin II arlcyude hrasvamaaya hraswa release kainattiksinte mutent roopathinte amithamaya aavishkaaram. deerghakaala release kainattiks fusion sushirathinte mandagathiyilulla adavine soochippikkunnu, athinaal chumbanam-oottam exocytosis samayat ethra neuro traansmittar purathuvarunnu ennathum myosin II niyanthrikkunnu.
kenikal.
chumbanam-aandu-rann exocytosisile kenii proteinukalude pankinekkurichu dhaaraalam pandithochithamaaya charchakal nilavilundu. kenii proteinukal vesicle fusion madhyasthatha vahikkunnu-fusion sushirathile presignaptic membranumaayi vesikkilukalude exocytosis. oru vesicle presignaptic membranumaayi samyojippikkumbol, oru trans sthaanathu ninnu oru sis sthaanathekku oru kenii parivartthanam sambhavikkunnu, thudarnnu kenii viyojip sambhavikkunnu. eee prakriya maattaanaavaathathaanennu karuthappettu. ennirunnaalum, chumbanam-oottam exocytosis sambhavikkukayaanenkil, kenii proteinukalude reversible association sambhavikkukayum exocytosisinte chumbanam-oottam modil madhyasthatha vahikkukayum cheiyunnuvennu ithu soochippikkunnu. chumbanam nadathumbol kenii proteinukalude krithrimathvam iva randum engane bandhappettirikkunnu ennathinekkurichu kooduthal ulkkaazhcha nalkukayum kooduthal pandithochithamaaya gaveshanam aavasyappedukayum cheyyum.