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EVA-1 Functions as an UNC-40 Co-receptor to Enhance Attraction to the MADD-4 Guidance Cue in


During animal development, cells and cell extensions migrate along stereotypical paths to their target destination by interacting with guidance cues in their environment. The guidance receptors on the surface of these cells can each interact with several different cues, and many of the cues can each interact with multiple receptors. How a migrating cell can reach its target amid this apparent receptor-cue promiscuity is poorly understood. Here, we extend our earlier investigation of how the UNC-40 receptor, which is known to interact with the UNC-6 guidance cue, mediates attraction towards the MADD-4 guidance cue. We show that another transmembrane protein called EVA-1 increases the sensitivity of UNC-40 to MADD-4. This increase in sensitivity allows UNC-40 to respond to MADD-4 in the presence of UNC-6. Without EVA-1, UNC-6 dominates UNC-40 function and restricts its response to MADD-4. Hence, the presence of EVA-1 acts like a switch to change UNC-40's sensitivity from UNC-6 to MADD-4, and in turn allows UNC-40-expressing cells to migrate towards the source of MADD-4 within a field of the UNC-6 guidance cue.


Vyšlo v časopise: EVA-1 Functions as an UNC-40 Co-receptor to Enhance Attraction to the MADD-4 Guidance Cue in. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004521
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004521

Souhrn

During animal development, cells and cell extensions migrate along stereotypical paths to their target destination by interacting with guidance cues in their environment. The guidance receptors on the surface of these cells can each interact with several different cues, and many of the cues can each interact with multiple receptors. How a migrating cell can reach its target amid this apparent receptor-cue promiscuity is poorly understood. Here, we extend our earlier investigation of how the UNC-40 receptor, which is known to interact with the UNC-6 guidance cue, mediates attraction towards the MADD-4 guidance cue. We show that another transmembrane protein called EVA-1 increases the sensitivity of UNC-40 to MADD-4. This increase in sensitivity allows UNC-40 to respond to MADD-4 in the presence of UNC-6. Without EVA-1, UNC-6 dominates UNC-40 function and restricts its response to MADD-4. Hence, the presence of EVA-1 acts like a switch to change UNC-40's sensitivity from UNC-6 to MADD-4, and in turn allows UNC-40-expressing cells to migrate towards the source of MADD-4 within a field of the UNC-6 guidance cue.


Zdroje

1. BonanomiD, PfaffSL (2010) Motor axon pathfinding. Cold Spring Harb Perspect Biol 2: a001735.

2. AhmedG, ShinmyoY, OhtaK, IslamSM, HossainM, et al. (2011) Draxin inhibits axonal outgrowth through the netrin receptor DCC. J Neurosci 31: 14018–14023.

3. HaddickPC, TomI, LuisE, QuinonesG, WranikBJ, et al. (2014) Defining the Ligand Specificity of the Deleted in Colorectal Cancer (DCC) Receptor. PLoS One 9: e84823.

4. DixonSJ, RoyPJ (2005) Muscle arm development in Caenorhabditis elegans. Development 132: 3079–3092.

5. WhiteJG, SouthgateE, ThomsonJN, BrennerS (1986) The structure of the nervous system of the nematode C. elegans. Philosophical Transactions of the Royal Society of London 314B: 1–340.

6. SeetharamanA, SelmanG, PuckrinR, BarbierL, WongE, et al. (2011) MADD-4 is a secreted cue required for midline-oriented guidance in Caenorhabditis elegans. Dev Cell 21: 669–680.

7. AlexanderM, ChanKK, ByrneAB, SelmanG, LeeT, et al. (2009) An UNC-40 pathway directs postsynaptic membrane extension in Caenorhabditis elegans. Development 136: 911–922.

8. AlexanderM, SelmanG, SeetharamanA, ChanKK, D'SouzaSA, et al. (2010) MADD-2, a homolog of the Opitz syndrome protein MID1, regulates guidance to the midline through UNC-40 in Caenorhabditis elegans. Dev Cell 18: 961–972.

9. WadsworthWG, BhattH, HedgecockEM (1996) Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin cues for guiding migrations in C. elegans. Neuron 16: 35–46.

10. YuTW, HaoJC, LimW, Tessier-LavigneM, BargmannCI (2002) Shared receptors in axon guidance: SAX-3/Robo signals via UNC-34/Enabled and a Netrin-independent UNC-40/DCC function. Nat Neurosci 5: 1147–1154.

11. ChanSS, ZhengH, SuMW, WilkR, KilleenMT, et al. (1996) UNC-40, a C. elegans homolog of DCC (Deleted in Colorectal Cancer), is required in motile cells responding to UNC-6 netrin cues. Cell 87: 187–195.

12. HedgecockEM, CulottiJG, HallDH (1990) The unc-5, unc-6, and unc-40 genes guide circumferential migrations of pioneer axons and mesodermal cells on the epidermis in C. elegans. Neuron 4: 61–85.

13. ZallenJA, YiBA, BargmannCI (1998) The conserved immunoglobulin superfamily member SAX-3/Robo directs multiple aspects of axon guidance in C. elegans. Cell 92: 217–227.

14. FujisawaK, WranaJL, CulottiJG (2007) The slit receptor EVA-1 coactivates a SAX-3/Robo mediated guidance signal in C. elegans. Science 317: 1934–1938.

15. HaoJC, YuTW, FujisawaK, CulottiJG, Gengyo-AndoK, et al. (2001) C. elegans slit acts in midline, dorsal-ventral, and anterior-posterior guidance via the SAX-3/Robo receptor. Neuron 32: 25–38.

16. HaoJC, AdlerCE, RobinsonD, GertlerFB, BargmannCI, et al. (2010) The Tripartite Motif Family Protein MADD-2 Functions with the receptor UNC-40/DCC in Netrin-Mediated Axon Attraction and Branching. Dev Cell 18: 950–960.

17. SongS, GeQ, WangJ, ChenH, TangS, et al. (2011) TRIM-9 functions in the UNC-6/UNC-40 pathway to regulate ventral guidance. J Genet Genomics 38: 1–11.

18. HamelinM, ZhouY, SuMW, ScottIM, CulottiJG (1993) Expression of the UNC-5 guidance receptor in the touch neurons of C. elegans steers their axons dorsally. Nature 364: 327–330.

19. LorenowiczM, MacurkovaM, HarterinkM, MiddelkoopT, BetistM, et al. (2014) Inhibition of late endosomal maturation restores Wnt secretion in C. elegans vps-29 retromer mutants. Cell Signal 26: 19–31.

20. HedgecockEM, CulottiJG, HallDH, SternBD (1987) Genetics of cell and axon migrations in Caenorhabditis elegans. Development 100: 365–382.

21. BrennerS (1974) The Genetics of Caenorhabditis elegans. Genetics 77: 71–94.

22. Ch'ngQ, WilliamsL, LieYS, SymM, WhangboJ, et al. (2003) Identification of genes that regulate a left-right asymmetric neuronal migration in Caenorhabditis elegans. Genetics 164: 1355–1367.

23. LewisJA, FlemingJT (1995) Basic culture methods. Methods Cell Biol 48: 3–29.

24. MelloCC, KramerJM, StinchcombD, AmbrosV (1991) Efficient gene transfer in C.elegans: extrachromosomal maintenance and integration of transforming sequences. Embo J 10: 3959–3970.

25. MitaniS (1995) Genetic regulation of mec-3 gene expression implicated in the specification of the mechanosensory neuron cell types in Caenorhaabditis elegans. Dev Growth & Diff 37: 551–557.

26. HofmannK, TschoppJ (1995) The death domain motif found in Fas (Apo-1) and TNF receptor is present in proteins involved in apoptosis and axonal guidance. FEBS Lett 371: 321–323.

27. McNeillH (2009) Planar cell polarity and the kidney. J Am Soc Nephrol 20: 2104–2111.

28. SuM, MerzDC, KilleenMT, ZhouY, ZhengH, et al. (2000) Regulation of the UNC-5 netrin receptor initiates the first reorientation of migrating distal tip cells in Caenorhabditis elegans. Development 127: 585–594.

29. DixonSJ, AlexanderM, FernandesR, RickerN, RoyPJ (2006) FGF negatively regulates muscle membrane extension in Caenorhabditis elegans. Development 133: 1263–1275.

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Genetika Reprodukčná medicína

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