Abstract
ARL15 is a member of the RAS superfamily of small GTPases and is associated with several metabolic traits, including increased risk of diabetes, rheumatoid arthritis and lipid metabolism disorders. The ARL15 gene encodes for an uncharacterized small GTP binding protein. Its precise role in human physiology remains unknown, but several genetic association studies have recognized different variants in this gene to be statistically associated with numerous traits and complex diseases. Here, we provided the unique features of ARL15 small G protein, its association with varied metabolic and lifestyle diseases, its function in vesicular and lipid trafficking, and its binding partners. We outlined this protein as a promising and emerging therapeutic target to combat metabolic disorders like cardiovascular diseases, diabetes and rheumatoid arthritis. The review provides a comprehensive description of the current advancements in ARL15 research with a perspective that focused research will position this small GTPase as a viable target for the treatment of rheumatoid arthritis.
Keywords: GTPase, ARF, ARL15, metabolic syndrome, rheumatoid arthritis, lipid trafficking, cardiovascular diseases.
[http://dx.doi.org/10.1126/stke.2502004re13] [PMID: 15367757]
[http://dx.doi.org/10.1242/jcs.01660] [PMID: 15731001]
[http://dx.doi.org/10.1096/fasebj.7.9.8330683] [PMID: 8330683]
[http://dx.doi.org/10.1016/B978-0-12-416749-0.00001-4] [PMID: 25033798]
[http://dx.doi.org/10.1038/nrm2476] [PMID: 18719708]
[http://dx.doi.org/10.1016/S0955-0674(99)80067-2] [PMID: 10449335]
[http://dx.doi.org/10.1016/S0960-9822(03)00069-1] [PMID: 12593809]
[http://dx.doi.org/10.1016/S0898-6568(00)00102-9] [PMID: 11027944]
[http://dx.doi.org/10.1186/1741-7007-10-71] [PMID: 22873208]
[http://dx.doi.org/10.1126/stke.2000.59.re1] [PMID: 11752622]
[http://dx.doi.org/10.1016/S0955-0674(00)00119-8] [PMID: 10873831]
[http://dx.doi.org/10.3389/fcell.2021.679046] [PMID: 34368129]
[http://dx.doi.org/10.1126/science.1068798] [PMID: 11923538]
[http://dx.doi.org/10.1016/0092-8674(92)90613-H] [PMID: 1606616]
[http://dx.doi.org/10.1096/fasebj.10.12.8903506] [PMID: 8903506]
[http://dx.doi.org/10.1074/jbc.M001027200] [PMID: 10843989]
[http://dx.doi.org/10.1002/anie.200600855] [PMID: 17031879]
[http://dx.doi.org/10.1042/BCJ20170015] [PMID: 28196833]
[http://dx.doi.org/10.1042/BC20060071] [PMID: 17155934]
[http://dx.doi.org/10.1083/jcb.200512057] [PMID: 16505163]
[http://dx.doi.org/10.1038/nrm3117] [PMID: 21587297]
[http://dx.doi.org/10.1016/j.bbamem.2004.04.005] [PMID: 15238254]
[http://dx.doi.org/10.1038/nsmb714] [PMID: 14718928]
[http://dx.doi.org/10.1074/jbc.M200128200] [PMID: 11847227]
[http://dx.doi.org/10.1083/jcb.149.5.1087] [PMID: 10831612]
[http://dx.doi.org/10.1074/jbc.M701347200] [PMID: 17452337]
[http://dx.doi.org/10.1111/cge.13541] [PMID: 30945270]
[http://dx.doi.org/10.1093/intimm/dxm154] [PMID: 18234692]
[http://dx.doi.org/10.1074/jbc.274.39.27553] [PMID: 10488091]
[http://dx.doi.org/10.1002/cm.20480] [PMID: 20740604]
[http://dx.doi.org/10.1074/jbc.M102359200] [PMID: 11303027]
[http://dx.doi.org/10.1016/j.febslet.2008.05.053] [PMID: 18588884]
[http://dx.doi.org/10.1091/mbc.e05-10-0929] [PMID: 16525022]
[http://dx.doi.org/10.1016/j.str.2005.11.008] [PMID: 16472755]
[http://dx.doi.org/10.1101/gad.173443.111] [PMID: 22085962]
[http://dx.doi.org/10.1016/j.cub.2007.03.007] [PMID: 17398095]
[http://dx.doi.org/10.1074/jbc.M002470200] [PMID: 10980193]
[http://dx.doi.org/10.1016/j.febslet.2004.04.048] [PMID: 15147902]
[http://dx.doi.org/10.1016/j.bbrc.2009.04.125] [PMID: 19409876]
[http://dx.doi.org/10.1083/jcb.20190509710072019c] [PMID: 31604800]
[http://dx.doi.org/10.1242/jcs.00123] [PMID: 12414990]
[http://dx.doi.org/10.1038/s41467-018-07444-y] [PMID: 30478271]
[http://dx.doi.org/10.1016/j.yexcr.2011.12.023] [PMID: 22245584]
[http://dx.doi.org/10.1016/j.jbc.2021.101422] [PMID: 34798070]
[http://dx.doi.org/10.1242/bio.201410975] [PMID: 25795912]
[http://dx.doi.org/10.1111/tra.12465] [PMID: 28000370]
[http://dx.doi.org/10.1016/j.cell.2010.05.015] [PMID: 20603001]
[http://dx.doi.org/10.1016/j.devcel.2014.09.004] [PMID: 25443296]
[http://dx.doi.org/10.1371/journal.pgen.1002358] [PMID: 22072986]
[http://dx.doi.org/10.1074/jbc.M109.070953] [PMID: 20207729]
[http://dx.doi.org/10.1016/j.bbrc.2006.03.221] [PMID: 16650381]
[http://dx.doi.org/10.1083/jcb.201607085] [PMID: 28325809]
[http://dx.doi.org/10.1242/jcs.01347] [PMID: 15331635]
[http://dx.doi.org/10.1016/j.devcel.2011.10.007] [PMID: 22172677]
[http://dx.doi.org/10.1016/j.immuni.2011.06.009] [PMID: 21802320]
[http://dx.doi.org/10.1242/jcs.02958] [PMID: 16537643]
[http://dx.doi.org/10.1242/jcs.162651] [PMID: 25908847]
[http://dx.doi.org/10.4049/jimmunol.1700829] [PMID: 29592961]
[http://dx.doi.org/10.1091/mbc.e13-05-0259] [PMID: 24088571]
[http://dx.doi.org/10.1074/jbc.RA117.000727] [PMID: 29618517]
[http://dx.doi.org/10.1056/NEJMoa042280] [PMID: 15843669]
[http://dx.doi.org/10.1073/pnas.1218272110] [PMID: 23223633]
[http://dx.doi.org/10.1242/jcs.143446] [PMID: 24777479]
[http://dx.doi.org/10.1016/j.devcel.2007.03.004] [PMID: 17488627]
[http://dx.doi.org/10.1371/journal.pgen.1003977] [PMID: 24339792]
[http://dx.doi.org/10.1242/dev.036350] [PMID: 19906870]
[http://dx.doi.org/10.1016/j.bbrc.2008.06.001] [PMID: 18554500]
[http://dx.doi.org/10.1073/pnas.1210916109] [PMID: 23150559]
[http://dx.doi.org/10.1016/j.devcel.2010.06.005] [PMID: 20643351]
[http://dx.doi.org/10.1016/j.cell.2013.08.060] [PMID: 24120134]
[http://dx.doi.org/10.1038/ejhg.2014.156] [PMID: 25138100]
[http://dx.doi.org/10.1016/j.cell.2011.03.023] [PMID: 21458045]
[http://dx.doi.org/10.1074/jbc.RA120.014999] [PMID: 32972971]
[http://dx.doi.org/10.1016/j.bbrc.2017.03.079] [PMID: 28322786]
[http://dx.doi.org/10.1007/s00018-021-03832-8] [PMID: 34089346]
[http://dx.doi.org/10.1074/jbc.M110.206896] [PMID: 21233210]
[http://dx.doi.org/10.1038/ncb1120] [PMID: 15077113]
[http://dx.doi.org/10.1016/S0960-9822(03)00089-7] [PMID: 12620188]
[http://dx.doi.org/10.1016/S0960-9822(03)00091-5] [PMID: 12620189]
[http://dx.doi.org/10.1242/jcs.02524] [PMID: 16129887]
[http://dx.doi.org/10.1371/journal.pgen.1000768] [PMID: 20011104]
[http://dx.doi.org/10.1038/srep45040] [PMID: 28452372]
[http://dx.doi.org/10.1681/ASN.2017030267] [PMID: 29093028]
[http://dx.doi.org/10.1016/j.gene.2018.08.041] [PMID: 30130595]
[http://dx.doi.org/10.7150/ijms.8206] [PMID: 24688318]
[http://dx.doi.org/10.1016/j.lfs.2019.01.030] [PMID: 30682341]
[http://dx.doi.org/10.1002/art.38110] [PMID: 23918589]
[http://dx.doi.org/10.1242/bio.058420] [PMID: 34779483]
[http://dx.doi.org/10.2337/db16-0361] [PMID: 27554474]
[PMID: 26722494]
[http://dx.doi.org/10.1146/annurev.cellbio.23.090506.123209] [PMID: 17506703]
[http://dx.doi.org/10.1038/nrdp.2018.14] [PMID: 29565029]
[http://dx.doi.org/10.1161/CIRCULATIONAHA.105.537878] [PMID: 15983262]
[http://dx.doi.org/10.1038/s41598-017-17746-8] [PMID: 29242557]
[http://dx.doi.org/10.1161/CIRCRESAHA.119.315246] [PMID: 31739742]
[http://dx.doi.org/10.1161/CIRCRESAHA.116.303603] [PMID: 25767291]
[http://dx.doi.org/10.1161/CIRCGENETICS.117.001811] [PMID: 29212900]
[http://dx.doi.org/10.1038/ng.2385] [PMID: 22885924]
[http://dx.doi.org/10.1016/j.mce.2018.06.003] [PMID: 29890211]
[http://dx.doi.org/10.1007/978-1-59745-245-8_1] [PMID: 18516549]
[http://dx.doi.org/10.1161/CIRCGENETICS.115.001246] [PMID: 26850992]
[http://dx.doi.org/10.1016/j.ajhg.2010.09.014] [PMID: 20950786]
[http://dx.doi.org/10.3390/ijms20194905] [PMID: 31623319]
[http://dx.doi.org/10.1038/ncomms13357] [PMID: 27876822]
[http://dx.doi.org/10.1038/nature09270] [PMID: 20686565]
[http://dx.doi.org/10.1016/j.drugalcdep.2014.05.023] [PMID: 24962325]
[http://dx.doi.org/10.1038/ng.2897] [PMID: 24509480]
[http://dx.doi.org/10.1001/jama.2015.3435] [PMID: 25919528]
[http://dx.doi.org/10.1038/gene.2011.30] [PMID: 21614018]
[http://dx.doi.org/10.3390/ijms20174091] [PMID: 31443349]
[http://dx.doi.org/10.1007/s12041-021-01286-2] [PMID: 34187973]
[PMID: 29382430]
[http://dx.doi.org/10.1016/S0140-6736(07)60784-3] [PMID: 17570481]
[http://dx.doi.org/10.1038/nrd.2016.21] [PMID: 27080040]
[http://dx.doi.org/10.1016/S0140-6736(10)60826-4] [PMID: 20870100]
[http://dx.doi.org/10.1093/oxfordjournals.bmb.a072958] [PMID: 7552061]
[http://dx.doi.org/10.1038/nrrheum.2012.153] [PMID: 23007741]
[http://dx.doi.org/10.1097/BOR.0000000000000470] [PMID: 29206659]
[http://dx.doi.org/10.1371/journal.pone.0057304] [PMID: 23468964]
[http://dx.doi.org/10.1097/BOR.0b013e32832a2e16] [PMID: 19318947]
[PMID: 24024009]
[http://dx.doi.org/10.1007/s11926-012-0275-1] [PMID: 22773387]
[http://dx.doi.org/10.1016/S0140-6736(17)31491-5] [PMID: 28612748]
[http://dx.doi.org/10.1038/ncprheum0562] [PMID: 17664952]
[http://dx.doi.org/10.1016/j.hcl.2010.09.002] [PMID: 21176795]
[http://dx.doi.org/10.1186/s13075-018-1645-5] [PMID: 30005689]
[http://dx.doi.org/10.1016/j.clinthera.2011.05.044] [PMID: 21704234]
[http://dx.doi.org/10.1186/1475-2840-11-151] [PMID: 23249664]
[http://dx.doi.org/10.1016/j.cytogfr.2012.07.004] [PMID: 22910140]
[http://dx.doi.org/10.1016/j.semarthrit.2008.01.017] [PMID: 18395775]
[http://dx.doi.org/10.1136/annrheumdis-2011-200924] [PMID: 22532632]
[http://dx.doi.org/10.1002/art.27450] [PMID: 20222108]
[PMID: 29465355]
[http://dx.doi.org/10.1177/1759720X10378372] [PMID: 22870451]
[http://dx.doi.org/10.1007/s12272-015-0569-8] [PMID: 25648633]
[http://dx.doi.org/10.1101/cshperspect.a016295] [PMID: 25190079]
[http://dx.doi.org/10.1186/ar1038] [PMID: 15059275]
[http://dx.doi.org/10.2741/1817]
[http://dx.doi.org/10.1002/jcb.23059] [PMID: 21321996]
[http://dx.doi.org/10.3390/ijms18050905] [PMID: 28441353]
[http://dx.doi.org/10.1172/JCI108195] [PMID: 1184744]
[http://dx.doi.org/10.1172/JCI0215528] [PMID: 12208866]
[http://dx.doi.org/10.1038/nature01661] [PMID: 12748655]
[http://dx.doi.org/10.1016/j.biopha.2018.07.027] [PMID: 30119166]
[http://dx.doi.org/10.1080/07391102.2020.1860826] [PMID: 33356902]
[http://dx.doi.org/10.1093/nar/gkv342] [PMID: 25883148]
[http://dx.doi.org/10.1002/prot.25414] [PMID: 29082551]
[http://dx.doi.org/10.1038/s41586-021-03819-2] [PMID: 34265844]
[http://dx.doi.org/10.1093/nar/gkm290] [PMID: 17517781]
[http://dx.doi.org/10.1093/nar/gkaa1074] [PMID: 33237311]