
cx3c muulaamsam chemokin grahakam 1

cx3sii motifku chendina chemokin receptor 1 (cx3cr1), dheenini fratalkin receptor ledhaa zii-protein coupled receptor 13 (gpr13) anie kooda pilustaaru, idhi zii protein-coupled receptor 1 (gpcr1) kutumbaaniki chendina transmembrane protein mariyu cx3sii chemokin receptor upakutumbamlo telisina ekaika sabhyudu.
paeru suuchimchinatlugaa, eee grahakam inflammatory chemokin cx3cl1 (elukalalo neurotactin ledhaa maanavulalo fractalkin anie kooda pilustaaru) nuu bandhistundi. eee antarjanyut ligand cx3cr1 graahakamtho matrame bandhistundi. Cx3cl1 thoo Cx3cr1 yokka paraspara charya leukocytela valasalu, samslaeshanha mariyu nilupudalaku madhyavartitvam cheyagaladu, endukante metaloproteinesses (mpps) dwara proteolysis kaaranamgaa fracatalkin pora-langaru protein (mcx3cl1) alaage cheelika karige anuvugaa (scx3cl1) untundi. chindinchina roopam sampradaaya chemotoxis anae chemotoxis yokka vilakshanhamaina paniteerunu nirvahistundi, ayithe pora-kattubadi unna protein diapedesis sulabhataram cheyadaaniki antukune anuvugaa pravartistundi.
cx3cl1-cx3cr1 aksham yokka rendu bhaagaswaamulu sareeram antataa hematopoietic mariyu nanhematopoitic kanaala nundi aneka kana rakaalapai untaaru. antekakunda, vaati pratyaekamaina kana vyakteekarana nirdishta kanajaalaalu mariyu avayavaalapai aadharapadi untundi, ivi jeeva karyakalapala yokka vistruta golaanni andistaayi. anduvalla, vaati vividha kriyaatmaka karyakalapalanu parigananaloki teesukunte, avi bahula neurodegenerative mariyu inflammatory desorderlatho paatu tumerigenesisto kooda mudipadi untaayi.
janyusaastram.
cx3cr1 kosam coding janyuvunu ippudu adhikarikamga daani proteinku samanamga pilustaaruh "cx3cr1 janyuvu", conny ippatikee "v28; ccrl1; gpr13; cmkdr1; gprv28; cmkbrl1" vanti itara paatha paerlatoe suuchimchavachchu. maanavulalo janyuvu yokka janyuvu sthaanam chromosome 3p22.2 yokka chinna chetiki untundi. idhi naalugu exanlu (okati matrame coding praantaanni kaligi untundi) mariyu moodu intronic muulakaalatoe koodi untundi. janyu kramam yokka vyakteekarana mugguru prothsaahakula dwara niyantrinchabadutundi.
cx3cr1 janyuvulo rendu missense utparivartanalu, grahakam yokka single nucleotide polymorphism (snp) yokka vaividhyaalu, protein yokka kriyaatmaka maarpuku baadhyata vahistaayi. eee vaividhyaala paerlu icchina pratyaamnaayam mariyu daani sthaanam nundi teesukobaddaayih valine nundi isolucin (v249i) mariyu thraeonine nundi methionin (t280m). cx3cr1 yokka polymorphism hridayanaala vyavasthaku sambandhinchina vyaadhulatoe mudipadi undhi (udhaa.zii. atherosclerosis), naadii vyavastha (udhaa.zii. algimers vyaadhi, sclerosis) ledhaa infections (udhaa.zii. systemic candidiasis.
Cx3cr1 janyuvu yokka orthologlu jantuvulalo, mukhyamgaa adhika kriyaatmaka saaruupyata kaligina ksheeradaalalo, antey chimpanji, kukka, pilli, eluka mariyu elukalalo kanipistaayi. eluka janyuvulo chromosome 9qf4loe mariyu eluka 8va chromosomelo 8q32 sthaanamlo orthologlu untaayi.
vyakteekarana.
cx3సిఆraa్1 anedi hematopoietic vamsam nundi vividha kanaalalo nirmanatmakamga ledhaa taapajanaka pratispandanalo vyakteekarinchabadutundi tii lymphocytelu, sahaja killer (enke) kanaalu, dendritic kanaalu, bii lymphocytelu, maast kanaalu, monocytelu, macrophaselu, neutrophils, microglia, osteoclastlu mariyu thrombocytelu. inca, eee grahakanni endothelial kanaalu, epithelial kanaalu, myositelu mariyu austrocytelu vanti nanhematopoetic kanajaalaalo kooda chudavachu. sareeramlo cx3cr1 samruddhini parigananaloki teesukunte, idhi konni rakaala praanaantaka kanaala dwara kooda vyakteekarinchabadutunda kanugonabadindi.
function.
cx3సిఆraa్1 grahakam jeevakriya panitiirutoe zii-protein chemokin grahaka kutumbamlo bhaagam. daani kanaantara signalling cascadelu manugada, valasalu mariyu vistaranalo unnatlugaa adhika kriyaaseela sthithi vaipu kakunda kana karyakalapalanu modulate cheyadaaniki baadhyata vahistaayi.
vaapu samayamlo roganirodhaka kanaalanu gurtinchadamlo, raktapravaahamlo cx3cl1-cx3cr1 aksham yokka paniteeru pradhanamgaa chemotoxis mariyu diapedesis dwara valasa velladam dwara roganirodhaka kanaalanu niyaminchadam. vaastavaaniki, vyadhikaaraka kaarakaalaku vyatiraekamgaa shotha nirodhaka pratispandanalo bhaagamgaa eee paatranu rakshanagaa pariganistaaru. ayithe, chaalaa roganirodhaka kanaalu mariyu proteinla vale, inflammatory ledhaa auto emmune vyaadhulalo, cx3cr1 signalling anedi konni vyaadhula pathophysiologytho mudipadi untundi.
eee grahakam yokka vyakteekarana lymphocytelatho mudipadi unnatlu kanipistundi. cx3cr1 kooda monocytela dwara vyakteekarinchabadutundi mariyu monocytela manugadalo pradhana paatra poeshistumdi. endothelial kanaalu mariyu monocytela madhya cx3cl1-cx3cr1 aksham dwara rakta naalaalaloo communication anedi extracellular matricks mariyu angiogenesis erpadataaniki baadhyata vahistundi. idhi choopabadindi, cx3cr1 anedi ippatike emuka majjalo unna monocytelanu nilupudala mariyu vidudala dwara prabhaavitam cheyagaladu. antekakunda emuka majjalo, cx3cr1 osteoclastlu mariyu osteoblastla bhedamlo paatra dwara emuka punarnirmananni prabhaavitam chestundi.
naadii vyavasthalo cx3cl1/cx3cr1 aksham paatra microglia karyakalapala niyantrana kosam microglia, neuroglia mariyu neuronla madhya communicationnu madhyavartitvam cheyadam, anduvalla eee aksham saareeraka sthithi aadhaaramgaa neurodegenerative mariyu neuroprotective functionnu poeshistumdi.
kendra naadii vyavasthalooni microglia vaari synaptic lakshyalaku valasa velladamlo fracatalkin signalling kooda abhivruddhi paatra pooshistundani iteevala kanugonabadindi, ikkada phagocytosis mariyu synaptic merugudala sambhavistaayi. cx3cr1 nakout elukalu adavi-rakam elukala kante hippocompal neuranlapy ekkuva synapses kaligi untaayi.
nirmaanam.
cx3cr1 anedi 355 amaino aamlaalatoe erpade samagra pora protein, dheeni paramaanu baruvu 40 kda untundi, idhi moodu pratyeka vibhaagaalanu kaligi untundih extra cellular, transmembrane mariyu intracellular bhaagam. gpcr kutumbamlo atipedda taragati sabhyudiga, rhodopsin lanty grahakaalu, grahakam yokka kanaantara bhaagam, polypeptide yokka sii-terminus mariyu moodu kanaantara looplu, heterotremeric zii protein kosam samrakshinchabadina drylive muulaamsamtoe kuudina sarihaddu pradaesam. eee kutumbaanni tii-transmembrane grahakaalu (7-tm) anie kooda pilustaaru, endukante 7 α-helix transmembrane protein, ivi pratyamnaayamgaa kanam yokka cytoplasmic poralo untaayi. cx3cr1 yokka bahya kana vaipu polypeptide golusu yokka n-terminus mariyu moodu bahya kana looplanu kaligi untundi, idhi daani pradhana ligand cx3cl1 kosam oka binding sthalaanni yerparustundi, conny ccl26 (eotoxin-3): fratalkin thoo poliste takkuva binding anubandhaanni kaligi untundi), immunoglobulins ledhaa antu agentlu.
signalling cascade.
cx3cl1-cx3cr1 aksham 'signalling daani agonist yokka binding dwara grahakanni sakriyam cheyadam dwara praarambhamavutundi. dheeni taruvaata moodu upabhaagaalu kaligina heterotremeric zii complexes yokka conformational maarpu mariyu bhaagam yokka vibhajana jarugutundihi α (alfa), β (beata) mariyu γ (gaama). aneka mukhyamaina signalling margalu zii protein (ga mariyu gbtg) yokka vaeru cheyabadina bhagala dwara prerepinchabadataayi, veetilo plc/pikesi maargam, paie3keey/eketi/nf kebi maargam, raas/raaf/meck/erk (mapk) maargam (ledhaa pii38 mariyu jnk) mariyu creb maargam vantivi unnaayi. perigina vistarana, manugada mariyu kanaala perugudala, jeevakriya niyantrana, valasa prerana, apoptosis nirodhakata mariyu harmonelu mariyu inflammatory cytokinla sraavam paramgaa aaa signalling cascadelanni vibhina cellular pravartanalu mariyu nibandhanalaku baadhyata vahistaayi. cx3సిఆraa్1 signalling cascades yokka utpattulu cx3సిఆraa్1 positive hematopoietic kanaala roganirodhaka pratispandanalo praamukhyatanu kaligi untaayi.
clinical praamukhyata.
cx3cr1 mariyu roganirodhaka kanaalu daani samruddhiga unna kana uparitala vyakteekarana kaaranamgaa balamgaa anusandhaaninchabadi unnaayi. anduvalla, roganirodhaka saktiki sambandhinchina vyaadhulalo cx3cr1 yokka clinical ardhaanni kanugonavacchu. cx3సిఆraa్1 prabhaavita shareera bhaagamlo roganirodhaka kanaala perukupovadaanni penchagaladu, idhi vyaadhi teevrataram cheyadaaniki daariteestundi. konni udaaharanalu alerjeelu, rheumatoid arthuritis, moothrapindaala vyaadhulu, deerghakaalika kaaleya vyaadhi ledhaa crone 's vyaadhi.
cx3సిఆraa్1 kooda hechaivi-1kii courceptor, mariyu eee janyuvulo konni vaividhyaalu hechaivi-1 sankramanaku ekkuva grahanaseelataku mariyu sahayala vegavantamaina purogatiki daariteestaayi.
endothelial kanaalu mariyu roganirodhaka kanaala madhya paraspara charyalo cx3cr1 pradhana paatra poeshistumdi kabatti, idhi dhamani godalapai (phalakam) vascular nirmaanaaniki sahaayapadutundi, anduvalla idhi atherosclerosistho mudipadi undhi. adanamgaa, idhi thrombosis, itara hridaya sambandha vyaadhulu ledhaa mastishka ischemiaku kooda daariteeyavachchu.
cx3cl1-cx3cr1 aksham microglianu sakriyam cheyadam dwara naraala vaapunu niyantrinche saamarthyaanni kaligi untundi. anduvalla medadu vyaadhulalo daani paatra rakshanaatmakamainadi conny hanikaram kooda kaavacchu. algimers vyaadhi, parkinsons vyaadhi ledhaa neuro cognitive hechaivi-dementia vanti microglia mariyu neurodegenerative rugmatala madhya sambandhaalu unnaayi. antekakunda, amyotrophic lateral sclerosis unna rogula manugada samayam mariyu purogati retunu savarinchadaaniki cx3సిఆraa్1 vaividhyaalu vivarinchabaddaayi.
cx3cr1loe utparivartanalu hip yokka dysplasiatho mudipadi untaayi.
homozygus cx3cr1-m280 mutation maanava monocyte manugadanu balaheenaparustundi mariyu maanava daihika candiasis phalitaanni ksheenimpajestundi.
mundu cheppinatlugaa, eee grahakam mariyu daani ligand osteoclastlu mariyu osteoblastla bhedam paramgaa emuka kanajaalam yokka jeevakriyaku mukhyamainavi. bolu emukala kriyaarahitam mariyu itara roganirodhaka kanaala perukupovadam bolu emukala vyaadhiki sambandhinchinavi.
fractalkin thoo kuudina cx3cr1 aneka rakaala cancerlalo kooda ardhavantamaina sthaanaanni kaligi undhi (udhaa.zii. neuroblastoma, prostate cancer, gastric adenocarcinoma ledhaa bii sell lymphomas) ikkada cx3cl1-cx3cr1 aksham double agent, idhi antitumoral prabhavalanu (neoplasmnu lakshyamgaa chesukovadaniki roganirodhaka kanaalanu prerepinchadam mariyu niyaminchadam) mariyu proteumoral prabhavalanu (praanaantaka kanaalalo mukhyamaina karyakalapalanu prerepinchadamh daadi, vistarana mariyu apoptosis nirodhakata, metastassisnu sulabhataram cheyadaaniki) andistundi. anduvalla, idhi cancerku chikitsa lakshyamgaa chaalaa saamarthyaanni kaligi undhi.

