chloride potassium simporter 5

potassium-chloride transporter member 5 (akah kCC2 mariyu slc12a5) anedi neuron-nirdishta chloride potassium simporter, idhi takkuva kanaantara chloride saandratalanu nirvahinchadam dwara neuronlalo chloride ayan pravanatanu sthaapinchadaaniki baadhyata vahistundi. idhi synaptic nirodham, exytotoxicity nundi cellular rakshanaku keelakamaina madhyavarti mariyu neuroplasticity yokka modulatorga kooda panicheyavacchu. potassium-chloride transporter member member dheeni ionic uparitalaalaku kCC2 (potassium chloride cottransporter 2), maanavulalo "slc12a5" janyuvu nundi janyu muulam kosam slc12a5 anae paerlatoe kooda pilustaaru.
eee ravaanaadaaru yokka takkuva vyakteekarana kaligina jantuvulu teevramaina motaru lopaalu, muurchaakaara charya mariyu spaastisitiini pradarsistaayi. keey. sii. sii puurtigaa laeni keey. sii. sii nakout jantuvulu, swaasakosha vaiphalyam kaaranamgaa maranaanantaram maranistaayi.
sthaanam.
keey. sii. sii. 2 anedi kendra naadii vyavastha antataa vyakteekarinchabadina neuron-nirdishta pora protein, indulo hippocompus, hypothalamous, brainstem mariyu ventral vennupamu yokka motonuranlu unnaayi.
upa kana sthaayilo, kCC2 somata yokka poralu mariyu neuronla dendritelalo kanugonabadindi, oxanlapy vyakteekaranaku etuvanti aadharalu laevu. keey. sii. sii. 2 gaba graahakaalato kuudukunnadigaa kooda choopabadindi, ivi kana pora antataa chloride ayan kadalikanu anumatinchadaaniki ligand-gated ayan chaanellugaa panicheestaayi. saadhaarana paristhitulalo, gaba graahakaala teravadam chloride ayanla hyperpolarising pravahanni post synaptic neuronlanu kaalpulu cheyakunda nirodhinchadaaniki anumatistundi.
dheeniki viruddhamgaa, kCC2 kooda uttejakaramaina synapses vadda collocalise cheyabadindani choopabadindi. atuvanti collocalisationku suuchimchina vivarana emitante exytotoxicityki vyatiraekamgaa keey. sii. sii. 2 yokka sambhaavya rakshana paatra. neuronal membraneloni ayan chaanella uttejakaramaina synaptic uddeepana kaaranamgaa ayan pravaham ayanla venta neeru laagabadatamtho kanaala dravaabhisarana vaapuku kaaranamavutundi. osmotic homeostasisnu tirigi sthaapinchadaaniki kanaala nundi adanapu ayaanlanu tolaginchadaaniki kCC2 sahaayapadavachhu.
nirmaanam.
keey. sii. sii anedi proteinla katayan-chloride cottransporter (sii. sii. sii) suupar familylo sabhyudu.
anni sisisi proteinla maadirigaane, taruvaata anedi 12 transmembrane domainlu mariyu enn-mariyu sii-terminal cytoplasmic domainlu rendintitho kuudina samagra pora protein. vegavantamaina niyantrana kosam neuron lopala kinases dwara terminal cytoplasmic domainlanu phosphorylate cheyavachu.
rendu isopharmlu kCC2a, kCC2b.
kCC2 yokka rendu isopharmlu unnaih kCC2a mariyu kCC2b. rendu isopharmlu isopharmlu janyuvu mariyu modati mrna exon yokka differential spliesing paie pratyaamnaaya promoterla nundi utpannamavutaayi. isopharmlu vaati enn-terminilo bhinnamgaa untaayi, rendu splies vaeriyantlaloo peddadigaa తరువాతఎ roopam untundi.
prasavaniki mundu mariyu prasavaanantara abhivruddhi samayamlo kCC2a sthaayilu saapekshamgaa sthiramgaa untaayi.
marovaipu, kCC2b, prasavapurva abhivruddhi samayamlo chaalaa arudugaa untundi mariyu prasavaanantara abhivruddhi samayamlo balamgaa niyantrinchabadutundi. prarambha neural networklalo inhibitory synapses yokka post synaptic prabhavalanu vidhvamsam cheyadam nundi parinati chendina neural networklalo hyperpolarising prabhaavaalaku ksheeradaalalo gamaninchina "abhivruddhi maarpu" kii kCC2b vyakteekarana yokka niyantrana baadhyata vahistundani bhaavistunnaaru.
kCC2b nakout elukalu kevalam functional kCC2a undatam valla prasavaanantara roeju 17 (p17) varaku jeevinchagalavu, conny avi takkuva shareera baruvu, motaru lopaalu mariyu saadhaarana muurchalanu pradarsistaayi. puurti taruvaata naakavutlu naakavutlu mariyu mariyu rendoo laevu) swaasa vaiphalyam kaaranamgaa puttina tarvaata maranistaayi.
oligomerization.
rendu keey. sii. sii. 2 isopharmlu neuronlalo chloride homeostasisnu nirvahinchadaaniki kana porapai itara keey-cl simportarlatho homomultimerlanu ledhaa heteromultimerlanu yerparustaayi. medadu kanajaalamlo keey. sii. sii. 2 thoo kuudina diamerlu, trimerlu mariyu tetramerlu gurtinchabaddaayi. naraala kanaalalo chloride ayan pravanata abhivruddhiki oligomer-monomer nishpatti paraspara sambandhamlo perugutundani gamaninchinanduna, oligomerization transporter function mariyu activationlo mukhyamaina paatra poeshistumdi.
vyakteekaranalo abhivruddhi maarpulu.
ksheerada pinda abhivruddhi samayamlo keey. sii. sii. 2 sthaayilu takkuvagaa untaayi, neural netvarklu inca sthaapinchabadutunnaayi mariyu neuronlu atyanta plaastik (maarchadaginavi). eee dasalo, takkuva kCC2 vyakteekarana mariyu adhika sthaayi nkCC1 (Na +/k + chloride cottransporter 1) anie piluvabade transporter kaaranamgaa kanaantara chloride ayan saandratalu ekkuvagaa untaayi, idhi chloride ayaanlanu kanaalaloki kadilistundi. anduvalla, pinda abhivruddhi samayamlo, chloride pravanata anedi nirodhaatmaka synapses vadda gaba grahakaalu mariyu glycine graahakaala uddeepana chloride ayanlu kanaala nundi bayataku pravahinchelaa chestundi, antargata neuronal vaataavaranaanni takkuva pratikuulamgaa chestundi (i.ii. idhi visraantigaa unna daanikante ekkuva depolarised). eee dasalo, gaba grahakaalu mariyu glycine grahakaalu post synaptic neuranlapy nirodhaka prabhavakaalugaa kakunda uttejakaramainavigaa panicheestaayi, phalitamgaa neural networkla vidhvamsam mariyu hyperrexibilityki daariteestundi.
prasavaanantara abhivruddhi samayamlo, keey. sii. sii. 2 sthaayilu balamgaa niyantrinchabadataayi, ayithe enkesi 1 sthaayilu taggutaayi. vyakteekaranalo eee maarpu neuronla lopala chloride ayan gaadata yokka abhivruddhi maarputho adhika kanaantara gaadata nundi takkuva kanaantara gaadataku paraspara sambandham kaligi untundi. samarthavantamgaa, chloride ayan gaadata tagginappudu, cellular pora antataa chloride pravanata tiragabadutundi, tadwara gaba grahakam mariyu glycine grahaka uddeepana chloride ayan pravaahaaniki kaaranamavutaayi, idhi antargata neuronal vaataavaranaanni marinta pratikuulamgaa chestundi (i.ii. idhi visraantigaa unna daanikante ekkuva hyperpolarised). idhi prarambha naadii abhivruddhi dasha yokka uttejakaramaina post synaptic pratispandanala nundi paripakvata antataa gamaninchina nirodhaka post synaptic pratispandanalaku nirodhaka synapses yokka abhivruddhi maarpu.
function.
prastuta saahityam keey. sii. sii. 2 neuronlalo moodu praathamika paatralanu pooshistundani suchistundihi
post synaptic nirodham.
kCC2 anedi potassium (k +)/chloride (cl−) simporter, idhi neuronlalo chloride homeostasisnu nirvahistundi. kendra naadii vyavasthalooni gaba grahakaalu mariyu glycine grahakaalu dwara shaastreeya post synaptic nirodhakataku keey. sii. sii. 2 charya dwara sthaapinchabadina electrochemical chloride pravanata keelakam. neuronla nundi chloride velikiteetanu nadapadaniki kCC2 Na +/k + pump dwara utpatti cheyabadina potassium pravanatanu upayogistundi. vaastavaaniki, neuronal k + pravanata yokka edainaa antaraayam parokshamgaa kCC2 kaaryaacharananu prabhaavitam chestundi.
neuronal nashtam taruvaata keey. sii. sii. 2 nashtam (i.ii. ischemia, vennupamu debbatinadam, kendra naadii vyavasthaku saareeraka gaayam) nirodhakata niyantrananu kolpovadam mariyu tadupari neuronal hyperexitability, motaru spasticity mariyu gaba grahakaalu mariyu glycine grahakaalu hyperpolarising nundi depolarising post synaptic prabhaavaalaku tirigi ravadam vanti muurcha vanti karyakalapala abhivruddhiki daariteestundi.
cellular rakshana.
adhika sthaayi uddeepana mariyu kriyaaseela ayan chaanalla dwara tadupari ionic pravaham ionic draavanaalatoe paatu dravaabhisarana-nirbandhita neeru neuranlaloki lagabadatam valla cellular vaapuku daariteestundi. eee drugvishayaanni exytotoxicity antaaru. keey. sii. sii. 2 kana-vaapu dwara sakriyam cheyabadindani choopabadindi, anduvalla adhika uddeepana kaalaala taruvaata adhika ayaanlanu tolaginchadamlo paatra poeshistumdi, tadwara sthiramaina-sthithi neuronal vaalyuumnu nirvahinchadaaniki mariyu kanaalu pagalakunda nirodhinchadaaniki.
post synaptic nirodham kosam chloride pravanatanu sthaapinchadam daani praathamika paatra ayinappatikee, keey. sii. sii. 2 uttejakaramaina synapses sameepamlo collolise cheyagaladane vaastavam kooda eee paatraku kaaranam kaavacchu.
padanirmaanam mariyu glutamatergic synapses yokka paniteeru.
chloride homeostasis dwara gabergic synapses saamarthyaanni niyantrinchadamtho paatu, kendra naadii vyavasthalo glutamatergic synapses yokka marphogenesis mariyu paniteerulo keey. sii. sii. 2 keelaka paatra poeshistumdi. keey. sii. sii nakout jantuvulalo hippocompal kanajaalampai adhyayanalu keey. sii. sii laeni neuronlu dendritic perugudalanu mariyu vaikalyamtho kuudina dendritic vennemukalanu kunchinchukupotayani choopinchaayi. cartical neuronlalo chaalaa uttejakaramaina synapsesnu host chese dendritic vennemukala nirmaanam mariyu paniteerulo taruvaata keelaka paatra pooshistundani iteevali adhyayanalu niruupistunnaayi. actin cytoskelitantho paraspara charya dwara, keey. sii. sii. 2 dendritic vennemukala lopala transmembrane proteinla vyaaptiki paramaanu avarodhaanni yerparustundi, tadwara yampa grahakaalu mariyu synaptic shakti yokka sthaanika nirbandhaanni niyantristundi.
neuronal gaayam taruvaata gamaninchina keey. sii. sii. 2 yokka down regulation, mariyu gaba-madhyavartitva synapses yokka paryavasanamga vidhvamsam maarpu, neuronal dii-deferentiation yokka oka amsam kaavacchu anie pratipaadinchabadindi. naadii vyavasthalo debbatinna bhagala bhedaanni tolaginchadam valla neuronal netvarklu adhika sthaayi plaastisiteeki tirigi raavadaaniki veelu kalpistundi, tadwara networklo jarigina nashtanni bharti cheyadaaniki manugadalo unna neuronlanu tirigi wire cheyavachu. adanamgaa, keey. sii. sii. 2 down regulationpy taggina glutamatergic transmission, maarina chloride velikiteeta kaaranamgaa taggina gaba transmissionnu bharti cheyadaaniki homeostatic prakriyagaa upayogapadutundi.
oncogenesis.
oncogenesis utparivartanalu peddapregu cancertho mudipadi untaayi.
niyantrana.
transcriptional regulation trickeby receptor signalling.
kendra naadii vyavastha gaayam taruvaata trickeby grahaka signalling transduction cascade (bdnf mariyu enti-4/5 dwara sakriyam cheyabadindi) dwara taruvaata transcriptionalga down regulated cheyabadutundi.
post-translational regulation phosphorylation.
phosphorylation phosphorylation nishkriyam chestundani ledhaa taggistundani saampradayakamgaa bhaavistaaru, ayithe kCC2 proteinpy vividha pradaesaalaloo phosphorylation vibhina niyantrana phalitaalanu nirnayistundani suuchimchadaaniki iteevali aadharalu unnaih
keey. sii. sii. 2 plasmalemma (nimishalu) vadda chaalaa ekkuva turnover retunu kaligi undhi, idhi phosphorylation vegavantamaina niyantranaku praathamika yantraamgaa panichestundani suuchistumdi.
kaaryaacharana-aadhaarita taggimpu niyantrana.
nmda grahaka charya mariyu mariyu + pravaahampai uttejakaramaina glutamate charya dwara taruvaata tagginchabadutundi. eee prakriyaloo prakriyaloo paie vegavantamaina defosphorylation mariyu taruvaata yokka calpine protease cheelika untaayi, idhi single partical trackingnu upayoginchi prayogaalalo pradarsinchinatlugaa, transporter yokka merugaina pora vyaapti mariyu endocytosisku daariteestundi.
glutamate vidudala uttejakaramaina synapses vadda matrame kakunda, neuronal nashtam ledhaa ischemic avamanamu tarvaata kooda sambhavistundi. anduvalla, kaaryaacharana-aadhaarita taggimpu anedi kendra naadii vyavastha gaayam taruvaata taruvaata taggimpu sambhavinche antarleena yantraangam kaavacchu.

