240:. RTN 3 and 4 have sequence identity more closely related at 73% than between 2 and 4 with only a 52% sequence identity. There is a divergence in sequence between reticulons as their splice isoforms can be variable, even in the same organism. This is consistent with the evolution of species and cell-specific roles for reticulons. The longest
308:
Overall, three models have been identified of RHD topology. One finding suggests that the amino-acid terminus and the 66-loop extend into the extracellular space. This would indicate that the hydrophobic region double-backs on itself in the membrane. Other data suggests that the amino-terminal is
711:
Through the RTNLB1 and RTNLB2 reticulon domain, their function is part of a larger protein system that moderates FLS2 secretion. Receptor trafficking is looked at through plant studies as an important process of receptor activity. The role of human reticulons which are involved in intracellular
496:
has been studied extensively to show that this protein (Nogo-A) was identified as an inhibitor of neurite outgrowth. More specifically, the 66-loop region (Nogo66) is a potent inhibitor of neurite growth. Many studies in animals have found that inhibition of a NogoA interaction has promoted
256:
The reticulon family contain a carboxy-terminal reticulon homology domain (RHD) that has two hydrophobic regions of 28-36 amino acids. Those regions are supposedly embedded in the membrane. Those regions are separated by the 60-70 amino acids of the hydrophilic loop. Following the loop is a
703:, was tagged to identify reticulon-like protein RTNLB1 and its homolog RTNLB2. When manipulating the expression levels of RTNLB1 and RTNLB2, signaling of the FLS2 receptor was interrupted. A serine cluster at the
1122:
Lee, Hyoung Yool; Bowen, Christopher Hyde; Popescu, George Viorel; Kang, Hong-Gu; Kato, Naohiro; Ma, Shisong; Dinesh-Kumar, Savithramma; Snyder, Michael; Popescu, Sorina
Claudia (2011-09-01).
627:. Most of what we know for plants can be derived from research from the latter, with little research on plants alone. The localization of some RTNs has been recognized in the tubules of
1256:
Tolley, Nicholas; Sparkes, Imogen A.; Hunter, Paul R.; Craddock, Christian P.; Nuttall, James; Roberts, Lynne M.; Hawes, Chris; Pedrazzini, Emanuela; Frigerio, Lorenzo (2008-01-01).
707:
of the protein is important for the FLS2 interaction. Although there is not a direct interference, RTNLB1 and RTNLB2 interact with newly created FLS2 to facilitate transport to the
273:
to humans. The hydrophobic region of the structure is abnormally long compared to other transmembrane domains. The structure of the reticulon may be related to the function of this
305:
side of the ER membrane and they are able to interact with other cytosolic proteins. N-terminal regions in reticulon proteins are diversified in interacting with other substrates.
764:
analysis has shown that increased expression of RTNLB13 decreases the likeliness of proteins to be soluble in the ER lumen. To further examine that location of RTNS are the
1052:
Sparkes, Imogen; Tolley, Nicholas; Aller, Isabel; Svozil, Julia; Osterrieder, Anne; Botchway, Stanley; Mueller, Christopher; Frigerio, Lorenzo; Hawes, Chris (2010-04-01).
451:. Additionally, reticulons may be used to shape coated protein vesicles by interacting with a component of the adaptor protein complex (which maintains the coat on the
351:
localization sequence, but the RHD hydrophobic region is able to target protein-RTN to the ER by green fluorescence. Without the RHD, there is no association with the
756:
of those cells. Additionally, an ER luminal marker was tagged to further show that when RTNLB13 was added, morphological changes existed in the lumen of the
761:
197:, have been tracked in all eukaryotic organisms that have been examined. The family of vertebrate proteins are called reticulons, and all other located
176:) exogenously suppresses reticulon 4C function and therefore may play a role in dictating membrane curvature through inhibition of reticulon function.
321:. This would allow them to not only look different at each location, but be able to carry different roles in the cell and in different cell types.
643:. Current research includes the search for Nogo-66 protein homologs in plants. There is also hope to determine the RHD domain receptor in plants.
236:(ER), it is proposed that reticulons have evolved with the eukaryotic endomembrane system. In mammals, there are four reticulon genes: RTN
1258:"Overexpression of a Plant Reticulon Remodels the Lumen of the Cortical Endoplasmic Reticulum but Does not Perturb Protein Transport"
1124:"Arabidopsis RTNLB1 and RTNLB2 Reticulon-Like Proteins Regulate Intracellular Trafficking and Activity of the FLS2 Immune Receptor"
394:
trafficking in and out of the cell through plasma membrane-associated proteins. Reticulons additionally aid in the formation of
452:
395:
248:
is absent in fish where regeneration of central nervous system is extensive. Reticulons can vary in function between species.
516:
There is increasing evidence that reticulons are involved with several different types of neurodegenerative diseases such as
949:
600:
584:
568:
552:
436:. They are additionally involved in intracellular trafficking. In one example, it was shown that increasing expression of
71:
700:
687:
232:
are not found in either archaea or bacteria. Because of their absence from prokaryotes and close association with the
1054:"Five Arabidopsis Reticulon Isoforms Share Endoplasmic Reticulum Location, Topology, and Membrane-Shaping Properties"
768:, the increased expression of RTNLB13 did not have an effect on the Golgi shape and secretion of a reporter protein.
749:
944:
724:
986:"Analysis of the reticulon gene family demonstrates the absence of the neurite growth inhibitor Nogo-A in fish"
223:
313:. All of these models suggest that reticulons may have different topologies at different regions such as the
215:
686:, and eventually the plasma membrane. Immune receptors that are related to the plasma membrane are called
639:
cisternae. Scientists have inferred that reticulons have a role in assembling the nuclear envelope during
544:
521:
517:
408:
244:, Nogo-A, has shown through studies that it can inhibit neurite outgrowth and regeneration. However, this
166:
67:
654:
Due to the lack of information of reticulons, scientists often study reticulon-like proteins. The genome
765:
757:
753:
728:
679:
636:
632:
475:
448:
433:
417:
387:
356:
352:
348:
344:
314:
233:
47:
660:
has at least 19 reticulon like proteins, and 15 of them have been explicitly identified. One study on
740:
656:
219:
201:
are called reticulon-like proteins. Some examples of explored reticulon genomes of eukaryotes are in
147:
124:
55:
336:
1231:
818:
696:
556:
548:
502:
40:
289:; however, they have additionally been found on cell surfaces in mammals and on the surface of
1323:
1287:
1279:
1223:
1205:
1161:
1143:
1091:
1073:
1008:
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340:
59:
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1197:
1151:
1135:
1081:
1065:
998:
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958:
915:
905:
800:
425:
262:
984:
Diekmann H, Klinger M, Oertle T, Heinz D, Pogoda HM, Schwab ME, Stuermer CA (August 2005).
1026:
683:
671:
486:
444:
391:
318:
290:
245:
241:
63:
528:
produces a pathological agent. Reticulons can interfere with those enzymes by decreasing
1218:
1185:
309:
intracellular. Lastly, a third model explains the 66-loop and amino-terminal domain are
1156:
1123:
1086:
1053:
920:
892:
791:
286:
121:
1317:
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51:
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in neural tissue. It was later renamed when it was proved to be associated with the
1308:
897:
712:
protein trafficking indicate the relationship between reticulons and plant RTNLBs.
560:
529:
406:
in mammalian cells, it does not allow for proper formation of membrane tubules. In
203:
543:
was depleted in
Alzheimer’s patients. Nonetheless, the exact relationship between
635:. However, research shows that the reticulons are restricted to the edges of the
692:
662:
588:
564:
490:
399:
361:
207:
62:
formation, and other processes yet to be defined. They have also been linked to
805:
786:
150:(RHD) while other parts of the protein may vary even within a single organism.
1201:
1186:"Functions of reticulons in plants: What we can learn from animals and yeasts"
1027:"Identification and Characterization of TMEM33 as a Reticulon-binding Protein"
732:
704:
628:
369:
298:
294:
258:
194:
153:
A peculiar feature of RTN4's isoform RTN4A (Nogo-A) is its ability to inhibit
143:
24:
1283:
1209:
1147:
1077:
910:
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985:
667:
479:
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78:
36:
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1227:
1165:
1139:
1095:
1069:
1012:
970:
929:
814:
675:
506:
90:
787:"A class of membrane proteins shaping the tubular endoplasmic reticulum"
583:
through two-hybrid screening. Lastly, reticulons can be associated with
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745:
716:
572:
429:
421:
365:
332:
302:
274:
190:
139:
117:
86:
43:
478:
to upregulate its sensitivity to stressors, which is able to modulate
261:. The amino-terminal domains are not similar to reticulons within the
66:
roles in inhibition of neurite outgrowth. Some studies link RTNs with
620:
547:
and reticulons is unknown. There may also be a link of reticulons to
525:
460:
229:
173:
135:
94:
82:
670:
and specific receptors. The regulation of receptor transport to the
432:
that are involved with vesicular formation and morphogenesis of the
945:"The endoplasmic reticulum: A dynamic and well connected organelle"
265:. However, the three-dimensional structure has been preserved from
720:
719:
can be compared to reticulons is in looking at reticulon-depleted
624:
616:
510:
270:
266:
162:
489:
roles in inhibition of neurite outgrowth. The longest isoform of
596:
580:
576:
537:
498:
437:
325:
158:
154:
131:
110:
106:
102:
98:
785:
Voeltz, GK; Prinz WA; Shibata Y; Rist JM; Rapoport TA (2006).
893:"The reticulons: a family of proteins with diverse functions"
416:
and associated proteins interferes with the formation of the
599:
were related to the severity of the disease. Additionally,
455:). Reticulons may also be involved with apoptosis. The RTN
347:
from several different methods. Reticulons do not have an
428:
reassembly. Reticulons have been found to interact with
146:
region of RTNs contains a highly conservative reticulon
744:(RTNLB13) were cloned. Those members were expressed in
443:
keeps transport of proteins from retrograding from the
157:
growth. This reticulon subform is curiously absent in
120:, with 21 having been identified in the commonly used
54:
curvature. In addition, reticulons may play a role in
595:
was found. In muscle biopsies of rats, the levels of
257:
carboxy-terminal tail which has a length of about 50
738:In another study, members of the RTN family of the
603:
could be predicted with increased expression of RTN
509:have begun to see if we can use this phenomenon in
1309:The structure and membrane topology of reticulons
762:Fluorescence recovery after photobleaching (FRAP)
886:
884:
882:
880:
878:
876:
874:
872:
870:
868:
866:
864:
862:
860:
858:
856:
854:
852:
735:and the localization of the FLS2 was defected.
678:. Membrane associated proteins travel from the
615:Knowledge of the reticulon is more advanced in
850:
848:
846:
844:
842:
840:
838:
836:
834:
832:
587:(ALS). In a mouse model, varied regulation of
943:Hawes C, Kiviniemi P, Keichbaumer, V (2015).
505:. Subsequently, clinical trials of anti-Nogo
8:
398:and membrane morphogenesis. When inhibiting
699:the FLAGELIN-SENSITIVE2 (FLS2) receptor, a
281:Localization in ER, N- and C-terminal ends
1273:
1217:
1155:
1085:
1002:
919:
909:
804:
567:. In the most common mutated protein in
563:against the isoform A-specific region of
386:Evidence shows that reticulons influence
1184:Nziengui, H.; Schoefs, B. (2009-02-01).
752:(YFP). The RTNLB13 was localized in the
165:known for the heightened ability of its
81:studied so far carry RTN genes in their
50:, primarily playing a role in promoting
777:
520:and amyotrophic lateral sclerosis. In
485:Reticulons have also been linked with
285:Reticulons are typically in the ER of
138:and are accordingly spliced into many
575:, there was an interaction with both
113:. Plants possess a greater number of
7:
1251:
1249:
1247:
1245:
1190:Cellular and Molecular Life Sciences
1179:
1177:
1175:
1117:
1115:
1113:
1111:
1109:
1107:
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1047:
1045:
950:Journal of Integrative Plant Biology
674:is important for the recognition of
293:where they inhibit axon growth. The
85:. The reticulons are absent only in
607:A in lower motor neuron syndromes.
359:in the following organisms: yeast,
355:. Reticulons have localized to the
14:
891:Yang YS, Strittmatter SM (2007).
748:epidermal cells with an attached
1275:10.1111/j.1600-0854.2007.00670.x
130:The genes possess a number of
1:
688:pattern recognition receptors
585:amyotrophic lateral sclerosis
569:hereditary spastic paraplegia
555:. The serum of patients with
553:hereditary spastic paraplegia
474:C has also been shown in the
193:, which range from 200-1,200
72:amyotrophic lateral sclerosis
532:levels. It was found in the
501:growth and recovery after a
324:The first reticulon protein
169:to regenerate after injury.
666:looks at transport between
466:, which is an inhibitor of
252:Reticulon protein structure
97:have four reticulon genes,
1340:
806:10.1016/j.cell.2005.11.047
750:yellow fluorescent protein
46:residing predominantly in
1202:10.1007/s00018-008-8373-y
727:was detected in modified
647:Reticulon-like proteins:
41:evolutionary conservative
911:10.1186/gb-2007-8-12-234
331:was characterized as an
224:Saccharomyces cerevisiae
216:Drosophila melanogaster
29:reticulon-like proteins
1140:10.1105/tpc.111.089656
1070:10.1105/tpc.110.074385
1128:The Plant Cell Online
1058:The Plant Cell Online
1004:10.1093/molbev/msi158
234:endoplasmic reticulum
48:endoplasmic reticulum
741:Arabidopsis thaliana
731:structures of those
657:Arabidopsis thaliana
611:Reticulons in plants
337:neuroendocrine cells
220:Arabidopsis thaliana
185:Evolutionary history
125:Arabidopsis thaliana
56:nuclear pore complex
697:protein microarrays
545:Alzheimer’s disease
522:Alzheimer’s disease
518:Alzheimer's disease
424:. It also disrupts
412:, removing RTNL RET
68:Alzheimer's disease
963:10.1111/jipb.12297
557:multiple sclerosis
549:multiple sclerosis
503:spinal cord injury
297:, loop region and
172:Transmembrane 33 (
690:(PRRs). Through
39:) are a group of
1331:
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709:plasma membrane.
426:nuclear envelope
291:oligodendrocytes
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672:plasma membrane
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536:of humans that
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487:oligodendrocyte
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319:plasma membrane
301:are all on the
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148:homology domain
64:oligodendrocyte
12:
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1303:External links
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1064:(4): 1333–43.
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997:(8): 1635–48.
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1033:. Retrieved
1021:
994:
989:
979:
957:(1): 50–62.
954:
948:
938:
901:
898:Genome Biol.
896:
796:
790:
780:
746:tobacco leaf
739:
737:
725:Fluorescence
714:
691:
684:Golgi bodies
661:
655:
653:
648:
631:forming the
614:
515:
484:
445:Golgi bodies
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208:Mus musculus
204:Homo sapiens
202:
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28:
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15:
904:(12): 234.
733:yeast cells
721:yeast cells
693:Arabidopsis
663:Arabadopsis
649:Arabidopsis
629:plant cells
459:C inhibits
362:Arabidopsis
311:cytoplasmic
259:amino acids
212:Danio rerio
195:amino acids
58:formation,
35:s in other
25:vertebrates
1035:2015-02-22
772:References
705:N-terminal
668:organelles
507:antibodies
409:C. elegans
392:Golgi-body
382:Mechanisms
370:Drosophila
299:C-terminal
295:N-terminal
199:eukaryotes
189:Reticulon
144:C-terminal
79:eukaryotes
37:eukaryotes
17:Reticulons
1284:1600-0854
1210:1420-682X
1148:1040-4651
1078:1040-4651
676:pathogens
559:contains
480:apoptosis
468:apoptosis
180:Structure
115:reticulon
1324:Proteins
1318:Category
1292:17980018
1236:30563495
1228:18989623
1219:11131481
1166:21949153
1096:20424177
1013:15858203
971:25319240
930:18177508
823:12760025
815:16469703
717:proteins
430:proteins
396:vesicles
377:Function
191:proteins
140:isoforms
118:isoforms
91:bacteria
52:membrane
44:proteins
1262:Traffic
1157:3203430
1087:2879755
921:2246256
682:to the
621:animals
573:spastin
453:vesicle
447:to the
422:mitosis
420:during
366:Xenopus
339:from a
333:antigen
303:cytosol
275:protein
246:isoform
242:isoform
230:genomes
136:introns
95:Mammals
87:archaea
83:genomes
60:vesicle
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625:plants
617:yeasts
526:enzyme
511:humans
271:plants
267:yeasts
263:family
228:These
222:, and
174:TMEM33
155:axonal
1232:S2CID
1030:(PDF)
819:S2CID
623:than
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1092:PMID
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565:RTN4
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801:doi
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589:RTN
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