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Tytuł pozycji:

The netrin receptor UNC-40/DCC assembles a postsynaptic scaffold and sets the synaptic content of GABA A receptors.

Tytuł:
The netrin receptor UNC-40/DCC assembles a postsynaptic scaffold and sets the synaptic content of GABA A receptors.
Autorzy:
Zhou X; Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, Institut NeuroMyoGène, 69008, Lyon, France.
Gueydan M; Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, Institut NeuroMyoGène, 69008, Lyon, France.
Jospin M; Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, Institut NeuroMyoGène, 69008, Lyon, France.
Ji T; Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, Institut NeuroMyoGène, 69008, Lyon, France.; Instrumental analysis center, Shanghai Jiao Tong University, 200240, Shanghai, China.
Valfort A; Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, Institut NeuroMyoGène, 69008, Lyon, France.; Center for clinical pharmacology, Saint Louis College of Pharmacy, 2 Pharmacy Place, Saint-Louis, MO 63110, USA.
Pinan-Lucarré B; Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, Institut NeuroMyoGène, 69008, Lyon, France. .
Bessereau JL; Univ Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5310, INSERM U 1217, Institut NeuroMyoGène, 69008, Lyon, France. .
Źródło:
Nature communications [Nat Commun] 2020 May 29; Vol. 11 (1), pp. 2674. Date of Electronic Publication: 2020 May 29.
Typ publikacji:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
Język:
English
Imprint Name(s):
Original Publication: [London] : Nature Pub. Group
MeSH Terms:
Caenorhabditis elegans/*metabolism
Caenorhabditis elegans Proteins/*metabolism
Cell Adhesion Molecules/*metabolism
Receptors, Cell Surface/*metabolism
Receptors, GABA-A/*metabolism
Synaptic Transmission/*physiology
Animals ; Axon Guidance/physiology ; Cell Adhesion Molecules, Neuronal/metabolism ; Cytoskeletal Proteins/metabolism ; Helminth Proteins/metabolism ; Membrane Proteins/metabolism ; Nerve Tissue Proteins/metabolism ; Neuromuscular Junction/metabolism ; Synapses/physiology
References:
Horn, K. E. et al. DCC expression by neurons regulates synaptic plasticity in the adult brain. Cell Rep. 3, 173–185 (2013). (PMID: 2329109310.1016/j.celrep.2012.12.005)
Kayser, M. S., Nolt, M. J. & Dalva, M. B. EphB receptors couple dendritic filopodia motility to synapse formation. Neuron 59, 56–69 (2008). (PMID: 18614029261778710.1016/j.neuron.2008.05.007)
Wang, Q. et al. Neuropilin-2/PlexinA3 receptors associate with GluA1 and mediate Sema3F-dependent homeostatic scaling in cortical neurons. Neuron 96, 1084–1098.e7 (2017). (PMID: 29154130572680610.1016/j.neuron.2017.10.029)
Poon, V. Y., Choi, S. & Park, M. Growth factors in synaptic function. Front. Synaptic Neurosci. 5, 6 (2013). (PMID: 24065916377623810.3389/fnsyn.2013.00006)
Hedgecock, E. M., Culotti, J. G. & Hall, D. H. 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 (1990). (PMID: 231057510.1016/0896-6273(90)90444-K)
Chisholm, A. D., Hutter, H., Jin, Y. & Wadsworth, W. G. The genetics of axon guidance and axon regeneration in Caenorhabditis elegans. Genetics 204, 849–882 (2016). (PMID: 28114100510586510.1534/genetics.115.186262)
Kennedy, T. E., Serafini, T., de la Torre, J. R. & Tessier-Lavigne, M. Netrins are diffusible chemotropic factors for commissural axons in the embryonic spinal cord. Cell 78, 425–435 (1994). (PMID: 806238510.1016/0092-8674(94)90421-9)
Serafini, T. et al. The netrins define a family of axon outgrowth-promoting proteins homologous to C. elegans UNC-6. Cell 78, 409–424 (1994). (PMID: 806238410.1016/0092-8674(94)90420-0)
Keino-Masu, K. et al. Deleted in Colorectal Cancer (DCC) encodes a netrin receptor. Cell 87, 175–185 (1996). (PMID: 886190210.1016/S0092-8674(00)81336-7)
Leonardo, E. D. et al. Vertebrate homologues of C. elegans UNC-5 are candidate netrin receptors. Nature 386, 833–838 (1997). (PMID: 912674210.1038/386833a0)
Boyer, N. P. & Gupton, S. L. Revisiting Netrin-1: One Who Guides (Axons). Front. Cell. Neurosci. 12, (2018).
Hong, K. et al. A ligand-gated association between cytoplasmic domains of UNC5 and DCC family receptors converts netrin-induced growth cone attraction to repulsion. Cell 97, 927–941 (1999). (PMID: 1039992010.1016/S0092-8674(00)80804-1)
Dominici, C. et al. Floor plate-derived netrin-1 is dispensable for commissural axon guidance. Nature 545, 350–354 (2017). (PMID: 28445456543859810.1038/nature22331)
Varadarajan, S. G. et al. Netrin1 produced by neural progenitors, not floor plate cells, is required for axon guidance in the spinal cord. Neuron 94, 790–799.e3 (2017). (PMID: 28434801557644910.1016/j.neuron.2017.03.007)
Yamauchi, K. et al. Netrin-1 derived from the ventricular zone, but not the floor plate, directs hindbrain commissural axons to the ventral midline. Sci. Rep. 7, 1–12 (2017). (PMID: 10.1038/s41598-016-0028-x)
Gujar, M. R., Sundararajan, L., Stricker, A. & Lundquist, E. A. Control of growth cone polarity, microtubule accumulation, and protrusion by UNC-6/Netrin and its receptors in Caenorhabditis elegans. Genetics 210, 235–255 (2018). (PMID: 30045855611695210.1534/genetics.118.301234)
Limerick, G. et al. A Statistically-Oriented Asymmetric Localization (SOAL) model for neuronal outgrowth patterning by Caenorhabditis elegans UNC-5 (UNC5) and UNC-40 (DCC) netrin receptors. Genetics 208, 245–272 (2018). (PMID: 2909288910.1534/genetics.117.300460)
Glasgow, S. D. et al. Activity-dependent Netrin-1 secretion drives synaptic insertion of GluA1-containing AMPA receptors in the hippocampus. Cell Rep. 25, 168–182.e6 (2018). (PMID: 3028202610.1016/j.celrep.2018.09.028)
Wadsworth, W. G., Bhatt, H. & Hedgecock, E. M. Neuroglia and pioneer neurons express UNC-6 to provide global and local netrin cues for guiding migrations in C. elegans. Neuron 16, 35–46 (1996). (PMID: 856208810.1016/S0896-6273(00)80021-5)
Chan, S. S.-Y. et al. 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 (1996). (PMID: 886190310.1016/S0092-8674(00)81337-9)
Dixon, S. J. & Roy, P. J. Muscle arm development in Caenorhabditis elegans. Development 132, 3079–3092 (2005). (PMID: 1593010010.1242/dev.01883)
Seetharaman, A. et al. MADD-4 Is a secreted cue required for midline-oriented guidance in Caenorhabditis elegans. Dev. Cell 21, 669–680 (2011). (PMID: 2201452310.1016/j.devcel.2011.07.020)
Alexander, M. et al. An UNC-40 pathway directs postsynaptic membrane extension in Caenorhabditis elegans. Development 136, 911–922 (2009). (PMID: 1921167510.1242/dev.030759)
Colón-Ramos, D. A., Margeta, M. A. & Shen, K. Glia promote local synaptogenesis through UNC-6 (Netrin) signaling in C. elegans. Science 318, 103–106 (2007). (PMID: 17916735274108910.1126/science.1143762)
Stavoe, A. K. H. & Colón-Ramos, D. A. Netrin instructs synaptic vesicle clustering through Rac GTPase, MIG-10, and the actin cytoskeleton. J. Cell Biol. 197, 75–88 (2012). (PMID: 22451697331779910.1083/jcb.201110127)
Weinberg, P., Berkseth, M., Zarkower, D. & Hobert, O. Sexually dimorphic unc-6/Netrin expression controls sex-specific maintenance of synaptic connectivity. Curr. Biol. 28, 623–629.e3 (2018). (PMID: 29429615582012310.1016/j.cub.2018.01.002)
Tu, H., Pinan-Lucarré, B., Ji, T., Jospin, M. & Bessereau, J.-L. C. elegans punctin clusters GABAA receptors via neuroligin binding and UNC-40/DCC recruitment. Neuron 86, 1407–1419 (2015). (PMID: 2602857510.1016/j.neuron.2015.05.013)
Pinan-Lucarré, B. et al. C. elegans Punctin specifies cholinergic versus GABAergic identity of postsynaptic domains. Nature 511, 466–470 (2014). (PMID: 2489618810.1038/nature13313)
Apte, S. S. A Disintegrin-like and Metalloprotease (Reprolysin-type) with Thrombospondin Type 1 Motif (ADAMTS) superfamily: functions and mechanisms. J. Biol. Chem. 284, 31493–31497 (2009). (PMID: 19734141279721810.1074/jbc.R109.052340)
Dow, D. J. et al. ADAMTSL3 as a candidate gene for schizophrenia: Gene sequencing and ultra-high density association analysis by imputation. Schizophrenia Res. 127, 28–34 (2011). (PMID: 10.1016/j.schres.2010.12.009)
Zhou, X. & Bessereau, J.-L. Molecular architecture of genetically-tractable GABA Synapses in C. elegans. Front. Mol. Neurosci. 12, 304 (2019). (PMID: 31920535692009610.3389/fnmol.2019.00304)
Maro, G. S. et al. MADD-4/punctin and neurexin organize C. elegans GABAergic postsynapses through neuroligin. Neuron 86, 1420–1432 (2015). (PMID: 26028574467274010.1016/j.neuron.2015.05.015)
Tong, X.-J., Hu, Z., Liu, Y., Anderson, D. & Kaplan, J. M. A network of autism linked genes stabilizes two pools of synaptic GABAA receptors. eLife 4, e09648 (2015). (PMID: 26575289464292610.7554/eLife.09648)
Gally, C. & Bessereau, J.-L. GABA is dispensable for the formation of junctional GABA receptor clusters in Caenorhabditis elegans. J. Neurosci. 23, 2591–2599 (2003). (PMID: 12684444674207910.1523/JNEUROSCI.23-07-02591.2003)
Hoskins, R., Hajnal, A. F., Harp, S. A. & Kim, S. K. The C. elegans vulval induction gene lin-2 encodes a member of the MAGUK family of cell junction proteins. Development 122, 97–111 (1996). (PMID: 8565857)
Wu, G.-H., Muthaiyan Shanmugam, M., Bhan, P., Huang, Y.-H. & Wagner, O. I. Identification and characterization of LIN-2(CASK) as a regulator of Kinesin-3 UNC-104(KIF1A) motility and clustering in neurons. Traffic 17, 891–907 (2016). (PMID: 2717232810.1111/tra.12413)
Gitai, Z., Yu, T. W., Lundquist, E. A., Tessier-Lavigne, M. & Bargmann, C. I. The netrin receptor UNC-40/DCC stimulates axon attraction and outgrowth through enabled and, in parallel, Rac and UNC-115/AbLIM. Neuron 37, 53–65 (2003). (PMID: 1252677210.1016/S0896-6273(02)01149-2)
Gamblin, C. L. et al. Oligomerization of the FERM-FA protein Yurt controls epithelial cell polarity. J. Cell Biol. 217, 3853–3862 (2018). (PMID: 30082297621972510.1083/jcb.201803099)
Hirano, Y. et al. Structural basis of cargo recognition by the myosin-X MyTH4–FERM domain. EMBO J. 30, 2734–2747 (2011). (PMID: 21642953315530810.1038/emboj.2011.177)
Wei, Z., Yan, J., Lu, Q., Pan, L. & Zhang, M. Cargo recognition mechanism of myosin X revealed by the structure of its tail MyTH4-FERM tandem in complex with the DCC P3 domain. PNAS 108, 3572–3577 (2011). (PMID: 2132123010.1073/pnas.1016567108)
Stein, E., Zou, Y., Poo, M. & Tessier-Lavigne, M. Binding of DCC by Netrin-1 to mediate axon guidance independent of adenosine A2B receptor activation. Science 291, 1976–1982 (2001). (PMID: 1123916010.1126/science.1059391)
Chen, C.-H., He, C.-W., Liao, C.-P. & Pan, C.-L. A Wnt-planar polarity pathway instructs neurite branching by restricting F-actin assembly through endosomal signaling. PLoS Genet. 13, (2017).
Wang, X. et al. Transmembrane protein MIG-13 links the Wnt signaling and Hox genes to the cell polarity in neuronal migration. PNAS 110, 11175–11180 (2013). (PMID: 2378477910.1073/pnas.1301849110)
Goldman, J. S. et al. Netrin-1 promotes excitatory synaptogenesis between cortical neurons by initiating synapse assembly. J. Neurosci. 33, 17278–17289 (2013). (PMID: 24174661661836310.1523/JNEUROSCI.1085-13.2013)
Finci, L., Zhang, Y., Meijers, R. & Wang, J.-H. Signaling mechanism of the netrin-1 receptor DCC in axon guidance. Prog. Biophys. Mol. Biol. 118, 153–160 (2015). (PMID: 25881791453781610.1016/j.pbiomolbio.2015.04.001)
Antoine-Bertrand, J., Ghogha, A., Luangrath, V., Bedford, F. K. & Lamarche-Vane, N. The activation of ezrin–radixin–moesin proteins is regulated by netrin-1 through Src kinase and RhoA/Rho kinase activities and mediates netrin-1–induced axon outgrowth. Mol. Biol. Cell 22, 3734–3746 (2011). (PMID: 21849478318302610.1091/mbc.e10-11-0917)
Zhuang, B., Su, Y. S. & Sockanathan, S. FARP1 promotes the dendritic growth of spinal motor neuron subtypes through transmembrane Semaphorin6A and PlexinA4 signaling. Neuron 61, 359–372 (2009). (PMID: 19217374265478310.1016/j.neuron.2008.12.022)
Cheadle, L. & Biederer, T. Activity-dependent regulation of dendritic complexity by semaphorin 3A through Farp1. J. Neurosci. 34, 7999–8009 (2014). (PMID: 24899721404425610.1523/JNEUROSCI.3950-13.2014)
Toyofuku, T. et al. FARP2 triggers signals for Sema3A-mediated axonal repulsion. Nat. Neurosci. 8, 1712 (2005). (PMID: 1628692610.1038/nn1596)
Cheadle, L. & Biederer, T. The novel synaptogenic protein Farp1 links postsynaptic cytoskeletal dynamics and transsynaptic organization. J. Cell Biol. 199, 985–1001 (2012). (PMID: 23209303351822110.1083/jcb.201205041)
Kuo, Y.-C. et al. Structural analyses of FERM domain-mediated membrane localization of FARP1. Sci. Rep. 8, 10477 (2018). (PMID: 29992992604128610.1038/s41598-018-28692-4)
Biederer, T. & Südhof, T. C. CASK and protein 4.1 support F-actin nucleation on neurexins. J. Biol. Chem. 276, 47869–47876 (2001). (PMID: 1160439310.1074/jbc.M105287200)
Hsueh, Y.-P. et al. Direct interaction of CASK/LIN-2 and syndecan heparan sulfate proteoglycan and their overlapping distribution in neuronal synapses. J. Cell Biol. 142, 139–151 (1998). (PMID: 9660869213302710.1083/jcb.142.1.139)
Chen, K. & Featherstone, D. E. Pre and postsynaptic roles for Drosophila CASK. Mol. Cell. Neurosci. 48, 171–182 (2011). (PMID: 2182005410.1016/j.mcn.2011.07.009)
Hsueh, Y.-P., Wang, T.-F., Yang, F.-C. & Sheng, M. Nuclear translocation and transcription regulation by the membrane-associated guanylate kinase CASK/LIN-2. Nature 404, 298 (2000). (PMID: 1074921510.1038/35005118)
Wang, T.-F. et al. Identification of Tbr-1/CASK complex target genes in neurons. J. Neurochemistry 91, 1483–1492 (2004). (PMID: 10.1111/j.1471-4159.2004.02845.x)
Bamber, B. A., Beg, A. A., Twyman, R. E. & Jorgensen, E. M. The Caenorhabditis elegans unc-49 locus encodes multiple subunits of a heteromultimeric GABA receptor. J. Neurosci. 19, 5348–5359 (1999). (PMID: 10377345678232310.1523/JNEUROSCI.19-13-05348.1999)
Fritschy, J.-M., Harvey, R. J. & Schwarz, G. Gephyrin: where do we stand, where do we go? Trends Neurosci. 31, 257–264 (2008). (PMID: 1840302910.1016/j.tins.2008.02.006)
Tyagarajan, S. K. & Fritschy, J.-M. Gephyrin: a master regulator of neuronal function? Nat. Rev. Neurosci. 15, 141–156 (2014). (PMID: 2455278410.1038/nrn3670)
Yamasaki, T., Hoyos-Ramirez, E., Martenson, J. S., Morimoto-Tomita, M. & Tomita, S. GARLH family proteins stabilize GABAA receptors at synapses. Neuron 93, 1138–1152.e6 (2017). (PMID: 28279354534747310.1016/j.neuron.2017.02.023)
Davenport, E. C. et al. An essential role for the tetraspanin LHFPL4 in the cell-type-specific targeting and clustering of synaptic GABAA receptors. Cell Rep. 21, 70–83 (2017). (PMID: 28978485564080710.1016/j.celrep.2017.09.025)
Kneussel, M. et al. Loss of postsynaptic GABAA receptor clustering in gephyrin-deficient mice. J. Neurosci. 19, 9289–9297 (1999). (PMID: 10531433678293810.1523/JNEUROSCI.19-21-09289.1999)
Lévi, S., Logan, S. M., Tovar, K. R. & Craig, A. M. Gephyrin is critical for glycine receptor clustering but not for the formation of functional GABAergic synapses in hippocampal neurons. J. Neurosci. 24, 207–217 (2004). (PMID: 14715953672957910.1523/JNEUROSCI.1661-03.2004)
Crestani, F. et al. Trace fear conditioning involves hippocampal α5 GABAA receptors. Proc. Natl Acad. Sci. USA 99, 8980–8985 (2002). (PMID: 1208493610.1073/pnas.142288699)
Loebrich, S., Bähring, R., Katsuno, T., Tsukita, S. & Kneussel, M. Activated radixin is essential for GABAA receptor α5 subunit anchoring at the actin cytoskeleton. EMBO J. 25, 987–999 (2006). (PMID: 16467845140972210.1038/sj.emboj.7600995)
Serwanski, D. R. et al. Synaptic and non-synaptic localization of GABAA receptors containing the α5 subunit in the rat brain. J. Comp. Neurol. 499, 458–470 (2006). (PMID: 16998906274929210.1002/cne.21115)
Loh, K. H. et al. Proteomic analysis of unbounded cellular compartments: synaptic clefts. Cell 166(1295-1307), e21 (2016).
Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71–94 (1974). (PMID: 43664761213120)
Bindels, D. S. et al. mScarlet: a bright monomeric red fluorescent protein for cellular imaging. Nat. Methods 14, 53–56 (2017). (PMID: 2786981610.1038/nmeth.4074)
El Mouridi, S. et al. Reliable CRISPR/Cas9 genome engineering in Caenorhabditis elegans using a single efficient sgRNA and an easily recognizable phenotype. G3 (Bethesda) 7, 1429–1437 (2017). (PMID: 10.1534/g3.117.040824)
Dickinson, D. J., Pani, A. M., Heppert, J. K., Higgins, C. D. & Goldstein, B. Streamlined genome engineering with a self-excising drug selection cassette. Genetics 200, 1035–1049 (2015). (PMID: 26044593457425010.1534/genetics.115.178335)
Frøkjær-Jensen, C., Davis, M. W., Ailion, M. & Jorgensen, E. M. Improved Mos1-mediated transgenesis in C. elegans. Nat. Methods 9, 117–118 (2012). (PMID: 22290181372529210.1038/nmeth.1865)
Frøkjær-Jensen, C. et al. Random and targeted transgene insertion in Caenorhabditis elegans using a modified Mos1 transposon. Nat. Meth 11, 529–534 (2014). (PMID: 10.1038/nmeth.2889)
Bolte, S. & Cordelières, F. P. A guided tour into subcellular colocalization analysis in light microscopy. J. Microscopy 224, 213–232.
Dunn, K. W., Kamocka, M. M. & McDonald, J. H. A practical guide to evaluating colocalization in biological microscopy. Am. J. Physiol. - Cell Physiol. 300, C723–C742 (2011). (PMID: 21209361307462410.1152/ajpcell.00462.2010)
Liewald, J. F. et al. Optogenetic analysis of synaptic function. Nat. Methods 5, 895–902 (2008). (PMID: 1879486210.1038/nmeth.1252)
Lainé, V., Frøkjær-Jensen, C., Couchoux, H. & Jospin, M. The α1 subunit EGL-19, the α2/δ subunit UNC-36, and the β subunit CCB-1 underlie voltage-dependent calcium currents in Caenorhabditis elegans striated muscle. J. Biol. Chem. 286, 36180–36187 (2011). (PMID: 21878625319612610.1074/jbc.M111.256149)
Zhou, X. et al. A novel bipartite UNC-101/AP-1 μ1 binding signal mediates KVS-4/Kv2.1 somatodendritic distribution in Caenorhabditis elegans. FEBS Lett. 590, 76–92 (2016). (PMID: 2676217810.1002/1873-3468.12043)
Gally, C., Eimer, S., Richmond, J. E. & Bessereau, J.-L. A transmembrane protein required for acetylcholine receptor clustering in Caenorhabditis elegans. Nature 431, 578–582 (2004). (PMID: 15457263378193910.1038/nature02893)
Grant Information:
P40 OD010440 United States OD NIH HHS
Substance Nomenclature:
0 (Caenorhabditis elegans Proteins)
0 (Cell Adhesion Molecules)
0 (Cell Adhesion Molecules, Neuronal)
0 (Cytoskeletal Proteins)
0 (Helminth Proteins)
0 (Lin-2 protein, C elegans)
0 (MADD-4 protein, C elegans)
0 (Membrane Proteins)
0 (Nerve Tissue Proteins)
0 (Receptors, Cell Surface)
0 (Receptors, GABA-A)
0 (UNC-40 protein, C elegans)
0 (neuroligin 1)
Entry Date(s):
Date Created: 20200531 Date Completed: 20200824 Latest Revision: 20210529
Update Code:
20240104
PubMed Central ID:
PMC7260190
DOI:
10.1038/s41467-020-16473-5
PMID:
32471987
Czasopismo naukowe
Increasing evidence indicates that guidance molecules used during development for cellular and axonal navigation also play roles in synapse maturation and homeostasis. In C. elegans the netrin receptor UNC-40/DCC controls the growth of dendritic-like muscle cell extensions towards motoneurons and is required to recruit type A GABA receptors (GABA A Rs) at inhibitory neuromuscular junctions. Here we show that activation of UNC-40 assembles an intracellular synaptic scaffold by physically interacting with FRM-3, a FERM protein orthologous to FARP1/2. FRM-3 then recruits LIN-2, the ortholog of CASK, that binds the synaptic adhesion molecule NLG-1/Neuroligin and physically connects GABA A Rs to prepositioned NLG-1 clusters. These processes are orchestrated by the synaptic organizer CePunctin/MADD-4, which controls the localization of GABA A Rs by positioning NLG-1/neuroligin at synapses and regulates the synaptic content of GABA A Rs through the UNC-40-dependent intracellular scaffold. Since DCC is detected at GABA synapses in mammals, DCC might also tune inhibitory neurotransmission in the mammalian brain.

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