Retikulon 4
(Preusmjereno sa Nogo)
Retikulon 4, znan i kao inhibitor izrastanja neurita ili Nogo, jest protein koji je kod ljudi kodiran genom RTN4 sa hromosoma 2.[5][6][7] Identificiran je an kao inhibitor izrastanja neurita specifičnog za centralni nervni sistem. Tokom nervnog razvoja, Nogo se uglavnom eksprimira putem neurona i pruža inhibitorni signal za migraciju i klijanje endotelnih (vrh) ćelija CNS-a, čime se ograničava gustoća krvnih sudova.
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 473 aminokiseline, a molekulska težina 50.708 Da.[7]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MKRASAGGSR | LLAWVLWLQA | WQVAAPCPGA | CVCYNEPKVT | TSCPQQGLQA | ||||
| VPVGIPAASQ | RIFLHGNRIS | HVPAASFRAC | RNLTILWLHS | NVLARIDAAA | ||||
| FTGLALLEQL | DLSDNAQLRS | VDPATFHGLG | RLHTLHLDRC | GLQELGPGLF | ||||
| RGLAALQYLY | LQDNALQALP | DDTFRDLGNL | THLFLHGNRI | SSVPERAFRG | ||||
| LHSLDRLLLH | QNRVAHVHPH | AFRDLGRLMT | LYLFANNLSA | LPTEALAPLR | ||||
| ALQYLRLNDN | PWVCDCRARP | LWAWLQKFRG | SSSEVPCSLP | QRLAGRDLKR | ||||
| LAANDLQGCA | VATGPYHPIW | TGRATDEEPL | GLPKCCQPDA | ADKASVLEPG | ||||
| RPASAGNALK | GRVPPGDSPP | GNGSGPRHIN | DSPFGTLPGS | AEPPLTAVRP | ||||
| EGSEPPGFPT | SGPRRRPGCS | RKNRTRSHCR | LGQAGSGGGG | TGDSEGSGAL | ||||
| PSLTCSLTPL | GLALVLWTVL | GPC |
Funkcija
urediOvaj gen pripada porodici retikulonskih kodirajućih gena. Retikuloni su povezani s endoplazmatskim retikulumom i uključeni su u neuroendokrinu sekreciju ili u membranski promet u neuroendokrinim ćelijamama. Proizvod ovog gena je moćan inhibitor rasta neurita koji takođe može pomoći u blokiranju regeneracije centralnog nervnog sistema kod viših kičmenjaka. Identificirane su alternativno prerađene varijante transkripta izvedene iz diferencijalne prerade i upotrebe diferencijalnog promotora i kodiranja različitih izoformi.[7] Postoje tri izoforme: Nogo A, B i C. Nogo- A ima dva poznata inhibitorna domena, uključujući amino-Nogo, na N-terminalu i Nogo-66, koji čini molekule vanćelijske petlje. I amino-Nogo i Nogo-66 su uključeni u inhibitorne odgovore, gdje je amino-Nogo jak inhibitor rasta neurita, a Nogo-66 uključen je u uništavanje konusa rasta.[8]
Istraživanja sugeriraju da će blokiranje Nogo-A tokom oštećenja neurona (od bolesti kao što je multipla skleroza) pomoći u zaštiti ili obnavljanju oštećenih neurona.[8][9] Istraživanje mehanizama djelovanja ovog proteina predstavlja veliki potencijal za liječenje autoimuno posredovanih demijelinizirajućih oboljenja i regeneracija povreda kičmene moždine. Također je utvrđeno da je ključni faktor u procesu u kojem fizička vježba poboljšava procese učenja i pamćenja u mozgu.[10] Također se pokazalo da Nogo-A negativno regulira rast i popravak krvnih sudova nakon ishemijskog moždanog udara. Genetička delecija i blokada Nogo-A, posredovana antitijelima doveli su do poboljšane revaskularizacije i funkcionalnog oporavka u eksperimentalnom mišjem modelu moždanog udara.[11][12][13] Moreover, vascular leakage, a major complication following stroke, was reduced following anti-Nogo-A antibody treatment.[14]
Interakcije
urediPokazalo se da retikulon 4 reaguje sa WWP1,[15] BCL2-liki 1[16] i Bcl-2.[16]
Također pogledajte
urediReference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000115310 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000020458 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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- ^ Yang J, Yu L, Bi AD, Zhao SY (June 2000). "Assignment of the human reticulon 4 gene (RTN4) to chromosome 2p14-->2p13 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 88 (1–2): 101–2. doi:10.1159/000015499. PMID 10773680. S2CID 37521141.
- ^ a b c "Entrez Gene: RTN4 reticulon 4".
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- ^ Sozmen EG, Rosenzweig S, Llorente IL, DiTullio DJ, Machnicki M, Vinters HV, et al. (December 2016). "Nogo receptor blockade overcomes remyelination failure after white matter stroke and stimulates functional recovery in aged mice". Proceedings of the National Academy of Sciences of the United States of America. 113 (52): E8453–E8462. doi:10.1073/pnas.1615322113. PMC 5206535. PMID 27956620.
- ^ Lee H, Raiker SJ, Venkatesh K, Geary R, Robak LA, Zhang Y, Yeh HH, Shrager P, Giger RJ (March 2008). "Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength". The Journal of Neuroscience. 28 (11): 2753–65. doi:10.1523/JNEUROSCI.5586-07.2008. PMC 6670664. PMID 18337405. Sažetak – Eurek Alert.
- ^ Rust R, Grönnert L, Gantner C, Enzler A, Mulders G, Weber RZ, et al. (July 2019). "Nogo-A targeted therapy promotes vascular repair and functional recovery following stroke". Proceedings of the National Academy of Sciences of the United States of America. 116 (28): 14270–14279. doi:10.1073/pnas.1905309116. PMC 6628809. PMID 31235580.
- ^ Rust, R; Grönnert, L; Weber, RZ; Mulders, G; Schwab, ME (September 2019). "Refueling the Ischemic CNS: Guidance Molecules for Vascular Repair". Trends in Neurosciences. 42 (9): 644–656. doi:10.1016/j.tins.2019.05.006. PMID 31285047. S2CID 195834057.
- ^ Rust, R; Gantner, C; Schwab, ME (January 2019). "Pro- and antiangiogenic therapies: current status and clinical implications". FASEB Journal. 33 (1): 34–48. doi:10.1096/fj.201800640RR. PMID 30085886. S2CID 51937342.
- ^ Rust R, Weber RZ, Grönnert L, Mulders G, Maurer MA, Hofer AS, et al. (December 2019). "Anti-Nogo-A antibodies prevent vascular leakage and act as pro-angiogenic factors following stroke". Scientific Reports. 9 (1): 20040. Bibcode:2019NatSR...920040R. doi:10.1038/s41598-019-56634-1. PMC 6934709. PMID 31882970.
- ^ Qin H, Pu HX, Li M, Ahmed S, Song J (Dec 2008). "Identification and structural mechanism for a novel interaction between a ubiquitin ligase WWP1 and Nogo-A, a key inhibitor for central nervous system regeneration". Biochemistry. 47 (51): 13647–58. doi:10.1021/bi8017976. PMID 19035836.
- ^ a b Tagami S, Eguchi Y, Kinoshita M, Takeda M, Tsujimoto Y (Nov 2000). "A novel protein, RTN-XS, interacts with both Bcl-XL and Bcl-2 on endoplasmic reticulum and reduces their anti-apoptotic activity". Oncogene. 19 (50): 5736–46. doi:10.1038/sj.onc.1203948. PMID 11126360.
Dopunska literatura
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