RnDSy-lu-2945 Periodic Table of Neurotrophic and Neurotactic Factors
I/II XXXII * Notes 1. CNTN1 has two isoforms that have open reading frames (ORFs) of 1007 amino acids (aa) and 627 aa. * * 1 35K 2 150K 2. Sema4F is found on oligodendrocytes and postsynaptic dendrites. G/ G 95 1 90 3. CNTN2 mutations are associated with epilepsy. 4. APP has multiple splice variants and cleavage-generated fragments. CNTN1 Sema4F 5. There are at least two splice variants for Nectin-1. One variant is secreted with a MW of approximately 52K–54K, while the other isoform is a transmembrane protein Contactin-1 Table 1. Families Semaphorin 4F truncated to 458 aa. Nectin-1 dimers are important for maximizing synapse size. 6. SYND3 is attached to 100K–120K of heparin sulfate, which binds to immobilized GDNF. GP135; F3; MYPCN SEMAM; SEMAW; M-SEMA-M; S4F 7. It has been suggested that GDNF signaling may require concurrent TGF-b signaling in select cell types. There are four traditional splice variants of GDNF, which are 159 aa, Notch-1; PTPRZ; NrCAM; Neurofascin 155; Additional Information in Notes Section I Contactin IX TNFRSF XVII IgCAM XXV SLIT 185 aa, 202 aa, and 228 aa in length. Additionally, an opposite-strand derived form of GDNF that translates into a 77 aa mature molecule also exists. L1CAM; Caspr1; TNC ligand unknown 8. In general, NRPs bind Semas, while PLXNs transduce the signal. Structure Tyrosine Kinase/ II L1CAM X Neurexophilin XVIII 9. PLXND1 plays a critical role in the development of basal ganglia glutamatergic signaling. III/IV Protein Kinase Superfamily XXVI LRRTM XXII/XXIII XXIV/XXV/XXVI XXVII/XXVIII/XXIX/XXX XXXI XXXI/XXXII 10. Sema4G is highly expressed in cerebellar Purkinje cells. * * * * * * * * * b 12. APLP-1 has one splice variant, which has an ORF that is 651 aa in length. Multiple cleavage isoforms arise during apoptosis. 3 130–140K 4 100–120K Molecule 135K Native MW III APP XI Type B Carboxypeptidase XIX EVA1 XXVII TGF- 5 90–110K 6 200–250K 7 18–22K 8 250K 9 200–210K 10 100–110K G/ G 90 1 97 Number 1 1 95 1 83 S 93 1▲ 96 1▲ 91 1 90 13. Nectin-3, which is postsynpatic, binds to presynaptic Nectin-1 in-trans. Binding of Nectin-3 to Nectin-2 occurs on endothelial cells during leukocyte migration. G/ G 95 ORF % aa IV Neurexin XII Glypican XX GDNF Receptor XXVIII Reticulon Protein 15. NRTN is a potent trophic factor for dopaminergic neurons. CNTN2 APP Sequence ID Nectin-1 SYND3 GDNF PLXNA1 PLXND1 Sema4G 17. Homodimeric, and not monomeric, Sema3A is active. The 95K Sema3A monomer can be cleaved between Arg555 and Gln556, generating a 65K–70K N-terminal and a (Human to Mouse) 33K–50K C-terminal fragment (note: some reports state the native MW of Sema3A is approximately 125K; thus, cleavage would generate an 80K–90K N-terminal fragment). Contactin-2 Amyloid b Abbreviated Poliovirus Receptor Syndecan-3 Glial Cell Line-Derived Plexin A1 Plexin D1 Semaphorin 4G Name CNTN1 V LRRIg Protein XIII ROBO XXI Tenascin XXIX VPS10P-Related Sortilin 18. Sema5a is secreted with a MW of approximately 110K. Sema5A interacts with heparin sulfate to promote cell attraction and with chrondroitin sulfate to promote cell TAG1; Axonin-1; AXT; TAX1; FAME5 Precursor Protein Related 1 N-Syndecan; SDC3; SDCN Neurotrophic Factor NOV; NOVP; PLXN1 PLEXD1 repulsion. ABPP; CVAP Contactin-1 Full Name CD111; PVRL1; PRR1; ATF1; ATF2; HFB1-GDNF; HSCR3 NCAM; NrCAM; PTPRZ; Neurocan; VI Notch XIV Type I Cadherin XXII Nectin XXX Neuropilin PVRR1; HVEC; HIgR Pleiotrophin; GDNF; NRTN; Sema3A, 3C, 3E, 3F, 5A, 5B, 6D; Sema3A, 3C, 3E, 4A; PLXNB2, B3 19. CNTN4 plays a key role in olfaction. There are three isoforms that have ORFs that are of 282 aa, 697 aa, and 698 aa in length. APP; L1CAM; Caspr2 GP135; F3; MYPCN Alternate Name ARTN; Sema5A a PLXNB1; NRP1, 2 NRP1; VEGF R2 CNTN2, 3, 4; DR6 (CD358); APLP-1, -2; GFR -1, -2; SYND3 20. APLP-2 is presynaptic while its trans-heterodimerizing partner, APLP-1 is postsynaptic. ITM2B, 2C; Integrin b1; Reelin; Ig/MAM/FNIII-Domain Nectin-3; FGF R1c; SynCAM3 Laminin; Slit2 Notch-1; PTPRZ; NrCAM; Neurofascin 155; VII b-NGF XV XXIII Nogo Receptor XXXI Plexin 21. LINGO-1 is a potential member of the Nogo-66 receptor complex. L1CAM; Caspr1; TNC Containing Proteins 23. Notch-1 undergoes cleavage at three sites: Arg1664, Gly1710 and Ala1720. * * * * * 11 145–155K 12 100–120K VIII Integrin a- and b-chain XVI Protocadherin a and g XXIV Syndecan Proteoglycan XXXII Semaphorin 13 80–95K 14 200–205K 15 12–14K 16 250K 17 95K 18 135K 24. Unlike many Integrins, ITGA1 contains an internal “I” domain that precludes proteolysis. G/ G 91 1 89 1 93 S▲ 94 S 86 1 97 S 95 1▲ 93 25. NGF R may be cleaved to generate a 20K and 25K intracellular domain fragment that exhibit growth arrest activity. Note: There is no association between families and color. 26. NLGNs are postsynaptic proteins that bind presynaptic b-Neurexins. If NLGN1 has a site-B insert of eight aa after Glu297, it will bind only to b-Neurexins. Structure Key If this site-B insert is absent, NLGN1 will bind to both a- and b-Neurexins. Functionally, NLGNS that contain the site-B insert promote synapse formation while those that lack it CNTN3 APLP-1 Receptors or Ligands Nectin-3 Slit1 NRTN PLXNA2 Sema3A Sema5A promote synapse size expansion. NLGN1 is considered to be a glutamatergic NLGN. Contactin-3 Amyloid b Precursor-like Monomer Heterodimer SS Disulfide Bond-Linked ▲ Hypothesized structure, based on Poliovirus Receptor SLIT Homolog 1 Neurturin Plexin A2 Semaphorin 3A Semaphorin 5A 27. GPC1 is believed to undergo cleavage to generate an 80K–100K soluble isoform. Protein 1 Related 3 BIG-1; PANG; PCS Homodimer G GPI-Linked 1 Single Pass (Type I) Transmembrane the structure of the other members in its SLIL1; MEGF4 NTN OCT; PLXN2 SEMA1; SEMAD; SEMAIII; COLL1; SEMAF; SemF 28. MDGA1 influences inhibitory synapse development by binding NLGN2 in-cis and blocking its association with NRXN in-trans. C30 CD113; PVRL3; PRR3; PVRR3 HH16; Hsema-1; Hsema-III PTPRG; APP; APLP-1 Homo-oligomer S Secreted 3 Single Pass (Type III) Transmembrane protein family. Glypican 1; GREM1; GFRa-1, -2; SYND3 Sema3A, 6A, 6B; PLXNA1, A3, B3; SYND3 29. There are more than 20 splice variants of FGF R1. FGF R1c exhibits an unusual activity profile. It is inactive when it binds to NCAM-1 in-cis; however, when it binds to poly- CNTN3, 4, 5; APP; APLP-2 Nectin-1, -2; SynCAM1, 3 ROBO1, 2; EVA1C NRP1, 2 PLXNA1, A2, A3, A4, B1, D1; NRP1 sialylated NCAM-1 in-trans, it is active. The presence of an “acid box” (aa 126–133) is essential for FGF R1c to interact with NCAM-1 and N-Cadherin. V V VI/VII VIII IX/X XI XII/XIII/XIV XV/XVI/XVII XVIII/XIX XX/XXI 30. The GDNF Receptor family member GFRAL (GDNF Receptor-a-like) has been shown to be a receptor for GDF-15 and play a putative role in obesity. 31. NLGNS help form synapses, and SynCAMs lock these synapses into place. SynCAM1 binds to SynCAM3 in-trans, but it interacts with ErbB3/Her3 and Integrin a6b4 in-cis. * * * * * * * * * * * * * * * * SynCAM1 forms glia:neuron bonds in-trans by homo-oligomerizing. Up to 50% of the MW of SynCAM1 is attributed to variable glycosylation and alternative splicing. 19 125–135K 20 120–135K 21 80–90K 22 63–66K 23 300K 24 240–250K 25 75K 26 110–120K 27 100–170K 28 135–140K 29 130–140K 30 50–60K 31 95–115K 32 190–210K 33 15–17K 34 220–240K 35 95K 36 140–150K 32. Proteolytic cleavage of Slit2 generates a 140K N-terminal and a 55K–60K C-terminal fragment. The 200K and 140K isoforms of Slit2 activate ROBOs. The 60K C-terminal G/ G 95 1 91 1 98 1 88 1 91 1 88 1SS 90 1 97 89 G 95 1/ 1 98 G 93 1 96 S 96 S 76 1▲ 94 S 97 3▲ 90 fragment binds to GPC1. Slit2 has two splice variants, which are 1521 aa and 1525 aa in length. 33. ARTN is associated with pain-sensing neurons. CNTN4 APLP-2 LINGO-1 AMIGO2 Notch-1 ITGA1 NGF R NLGN1 GPC1 MDGA1 FGF R1c GFRa-1 SynCAM1 Slit2 ARTN PLXNA3 Sema3C Sema5B 35. Sema3C is cleaved at Arg745 by ADAMTS1 to generate a highly active 94K–95K polypeptide. Contactin-4 Amyloid b Precursor-like LRR and Ig Domain Amphoterin-Induced Neurogenic Locus Notch Integrin a1 Nerve Growth Factor Neuroligin 1 Glypican 1 MAM Domain Containing Fibroblast Growth Factor Glial Cell Line-Derived Synaptic Cell Adhesion SLIT Homolog 2 Artemin Plexin A3 Semaphorin 3C Semaphorin 5B 36. Sema5B is believed to be a type III transmembrane protein (i.e. it resembles a type I transmembrane protein but lacks a signal sequence). BIG-2; AXCAM Protein 2 Containing Nogo Receptor- Gene and ORF 2 Homolog Protein 1 CD49a; VLA-1 Receptor NL1 GPI Anchor 1 Receptor 1c Neurotrophic Factor Molecule 1 SLIL3 Enovin; EVN; Neublastin SEX; PLXN3; PLXN4; XAP-6 SEMAE; SemE SEMAG; SemG 37. CNTN5 has two isoforms that have ORFs that are 998 aa and 911 aa in length. a APPH; APPL2; CDEBP; WALPLP2; Interacting Protein 1 Alivin-1; ALI1; DEGA TAN1 p75NTR; Gp80-LNGFR; GPIM; MAMDC3; GPI N-SAM; Flt-2; bFGF-R-1; CD331; Receptor 1 IGSF4A; CADM1; Necl-2; TSLC1; 38. NRXN1a has an SS4 site that lies between aa 1241–1270. Multiple isoforms have been reported including a 73K, 442 aa b-isoform that binds “B-site” positive NLGN1. APP; APLP-1 YWK-II Laminin; Collagen; TNFRSF16; CD271 NRXN1a, 1b, 2a, 2b, 3a, 3b; Slit1, 2; FGF basic and MAM Protein FLG; CEK RA175; ST17; BL2 Glypican 1; GREM1; GFRa-1, -3; SYND3 Sema3A, 3F, 5A, 5B; PLXNA1, D1; PLXNA1, A3 LERN1; LRRN6A Sema7A; Integrin b1 NLGN3 GDNF Ra-1; TRNR1; RETL1; ROBO1, 2; EVA1C; APP NRP1, 2 NRP1:NRP2 (heterodimer) NRXN1a promotes GABAergic synapse organization while NRXN1b promotes glutamatergic synapse organization. AMIGO CNTN1, 6; Delta; Jagged 1, 2 GFRA1 APP; APLP-1 NgR; NGF R; LINGO-1; NGF; BDNF; NLGN2 Nectin-1; NCAM-1; N-Cadherin; multiple Nectin-3; SynCAM2, 3; FARP1; CRTAM; 39. It has been suggested that LINGO-2 variation influences risk and onset age of essential tremor and Parkinson’s disease. NT-3, -4; SORT1; NgR FGFs ErbB3; Integrin a6b4 TROY; TrkB GDNF; Ret; NRTN; ARTN 40. AMIGO3 is thought to be a member of the NgR:TROY complex, which serves as the Nogo-66 receptor. * * * * * * * * * * * * * * * * 41. The b-NGF precursor consists of an N-terminal 14K proregion that is coupled to a 12K–13K mature region. When the 25K–30K proform is released, it binds to an 37 125–135K 38 150–200K 39 80K 40 50–52K 41 12–13K 42 120–140K 43 44–48K 44 90–120K 45 190–210K 46 125–130K 47 200K 48 58K 49 52K 50 200K 51 13–14K 52 240–250K 53 90–95K 54 110–125K NGF R:SORT1 complex and induces apoptosis. Mature b-NGF does not bind to this complex. ProNGF will also bind to TrkA. G/ G 90 1 97 1▲ 98 1 77 S 85 1 90 1▲ 69 1▲ 98 1 95 G 98 1 83 G 89 1 97 S▲ 94 S 64 1▲ 98 S 93 1 95 43. TROY is thought to be a marker for microglia but not macrophages. 44. NLGN2 is considered to be a GABAergic NLGN. Unlike most NLGNs, which are typically localized to postsynaptic membranes, retina NLGN is presynaptic. CNTN5 NRXN1a LINGO-2 AMIGO3 b-NGF ITGA6 TROY NLGN2 ROBO1 MDGA2 Ret GFRa-2 SynCAM2 Slit3 PSPN PLXNA4 Sema3D Sema6A 46. MDGA2 has two splice variants, which are 727 aa and 1025 aa in length. Contactin-5 Neurexin 1a LRR and Ig Domain Amphoterin-Induced b-Nerve Growth Factor Integrin a6 TNF Receptor Neuroligin 2 Roundabout Homolog 1 MAM Domain Containing Proto-Oncogene RTK Ret Glial Cell Line-Derived Synaptic Cell Adhesion SLIT Homolog 3 Persephin Plexin A4 Semaphorin 3D Semaphorin 6A 47. Ret has one splice variant, called Ret-9, that is 1072 aa in length. Ret can be cleaved after Asp707 and Asp1017. The fragment that lies between Ala708 and Asp1017 NB-2; HNB-2s Containing Nogo Receptor- Gene and ORF 3 NGF; NGFB; HSAN5B CD49f; VLA-6; Platelet gpl Superfamily, Member 19 DUTT1 GPI Anchor 2 CDHF12; CDHF16; HSCR1; Neurotrophic Factor Molecule 2 SLIL2; MEGF5 PSP PLEXA4 Sema-Z2; COLL2 SEMAQ; Sema-VIA; appears to be apoptotic. Interacting Protein 2 Alivin-3; ALI3 TAJ; TRADE; TNFRSF19 MAMDC1 MEN2A; MEN2B; MTC1; Receptor a2 IGSF4D; CADM2; Necl-3 SEMA1; HT018 48. GFR-a2 has two splice variants that are 331 aa and 359 aa in length. The shorter GFR-a2 isoform negatively regulates the activity of the full-length protein and the 359 aa APLP-1; L1CAM NLGN1, 2, 3, 4X, 4Y; NXPH1, 2, 3; NGF R; TrkA; Laminin; Integrin b1, b4, b6; NRXN1a, 1b, 2a, 2b, 3a, 3b; NRP1; ROBO2; exists in a complex for PTC-ELE1; RET51 ROBO1, 2 GFRa-4 Sema3A, 6A, 6B, 6D; NRP1 isoform. The GDNF Receptor family member GFRAL (GDNF Receptor-a-like) has been shown to be a receptor for GDF-15 and play a putative role in obesity. LRRTM1, 2, 4; Granuphilin LERN3; LRRN6C Integrin a9b1 Netrin-1; SynCAM1, 2, 4 NLGN3; MDGA1, 2 Sema3A and Sema3F; Slit1, 2, 3 GDNF Ra-2; GDNFRB; TRNR2; NRP1, 2 AMIGO; NgR LINGO-1:NgR complex NLGN2 a SynCAM1, 3, 4; Integrin a6b4 PLXNA2, A4 GFRa-1, -2, -3; PCDHA4; PCDHGB7 RETL2; GFRA2; NRTNR 49. Neuronal SynCAM2 interacts with SynCAM3 located on oligodendrocytes. ligand unknown GDNF; NRTN; Ret; NCAM-1 50. Slit3 has three splice variants, which are 1423 aa, 1472 aa, and 1530 aa in length. 51. The PSPN:GFRa-4 complex inefficiently recruits Ret. * * * * * * * * * * * * * 125–135K 182K 62K 140K 13K 150–160K 29–31K 110–125K 200–210K 120–130K 190K 50–56K 50–60K 70K 205–225K 250–270K 90–95K 100–110K 52. PLXNA4 mutations may be involved in the pathogenesis of familial Parkinson’s disease. PLXNA3 and PLXNA4 appear to regulate autonomic sympathetic neuron migration and 55 56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 neurite extension. G/ G 89 1▲ 98 1▲ 88 1 86 S/ S / S 97 1 89 S 99 1 96 1 94 1 86 1 89 G 76 1 95 1 97 76 1▲ 87 S 90 1 89 53. Sema3D is cleaved to generate a 65K–70K fragment that is necessary for full activity. CNTN6 NRXN2a LINGO-3 TrkA BDNF ITGA9 NXPH1 NLGN3 ROBO2 PCDHA4 c-MET GFRa-3 SynCAM3 LRRTM1 Nogo-A PLXNB1 Sema3E Sema6B 54. Sema6A mediates granule cell migration. Contactin-6 Neurexin 2a LRR and Ig Domain Neurotrophic Tyrosine Brain-Derived Integrin a9 Neurexophilin-1 Neuroligin 3 Roundabout Homolog 2 Protocadherin a4 Hepatocyte Growth Glial Cell Line-Derived Synaptic Cell Adhesion Leucine-rich Repeat Reticulon 4A Plexin B1 Semaphorin 3E Semaphorin 6B 56. The b splice variant of NRXN2 has a MW of 76K–80K, is 666 aa in length, and binds to NLGN1 proteins that contain the site-B insert. 59. The BDNF precursor consists of an N-terminal 16K–18K proregion that is coupled to a 13K mature region. When the 30K-32K proform is released, it binds to a NGF R:SORT1 NB3 Containing Nogo Receptor- Kinase Receptor A Neurotrophic Factor ITGA4L; RLC-a NPH1 ASPGX1; AUTSX1; HNL3; NL3; SAX3 CNRN1; CRNR1; CNR1 Factor Receptor Neurotrophic Factor Molecule 3 Transmembrane RTN4; RTN4A; NI220; SEP; PLXN5 SEMAH; M-SemaK; COLL5 SEMAN; Sema-VIB; SEM-SEMA-Y complex, which may also interact with TrkB. ProBDNF does not bind to Trk-B. There are four BDNF splice variants, which are 255 aa, 262 aa, 276 aa, and 329 aa in length. Interacting Protein 3 NTRK1; p140-TrkA; MTC Gliotactin HGF R; MET; AUTS9; RCCP2; Receptor a3 IGSF4B; CADM3; Necl-1; Neuronal 1 ASY; RTN-X; NSP Notch-1 GABA A Rg ; NLGN1, 2, 3; Integrin a9b1; NGF R; NCAM-1; TNC; TrkB; VCAM-1; OPN; NGF; BDNF; NRXN1a, 2a, 3a ROBO1; Slit1, 2, 3 Ret; PCDHGB7 Sema3A, 4C, 4D; PLXNA1, B2; c-MET; PLXNA1, D1; PLXNA2, A4 2 Scatter Factor Receptor TSLL1; BIgR 61. NXPHs appear to be secreted only by inhibitory neurons. NXPHs bind a-Neurexins while NLGNs bind b-Neurexins. ProNXPH1 has a MW of approximately 46–50K. LERN2; LRRN6B TrkB:TrkC (heterodimer); b GDNF Ra-3; GDNFR3; GFRA3 LRRT1; LRRTM Neuronal Protein 1 Dystroglycan; NXPH1, 2, 3 NGF; NT-3; SORT1 NT-3; Integrin 1; TNC NRXN1a, 1b, 2a, 2b, 3a, 3b; NgR NRP1, 2; ErbB2; MSP R NRP1; VEGF R2 NT-3, -4 (non-covalent heterodimers) NLGN1, 2 62. NLGN3 participates in both GABAergic and glutamatergic synapse development. ligand unknown HGF; PLXNB1, B2, B3; Sema4D ARTN; Ret SynCAM1, 2, 4; Nectin-1, -3 NRXN1a, 1b 64. PCDHA4 has only one alternative splice variant that is 798 aa in length. Cleavage of the full-length 120K protein is believed to generate a second isoform that contains a 75K soluble fragment plus a 40K transmembrane truncated segment. * * * * * * * * * * * * * * * 65. The c-MET precursor can be cleaved to generate a disulfide-linked heterodimer that consists of a 50K extracellular domain (ECD) and a 140K transmembrane/cytoplasmic 73 200–220K 74 178K 75 61K 76 145K 77 14K 78 120–140K 79 29K 80 105–115K 81 195–210K 82 110–120K 83 185K 84 30–32K 85 55–65K 86 75–80K 87 95–110K 88 240–250K 89 90K 90 110–120K segment. In general, there are more that 50 isoform variants of c-MET, many of which are presumed to be soluble. The name MET is derived from the first three letters 1 88 1 98 1▲ 94 1 94 S 96 1 92 S 89 1 57 1▲ 81 1 82 1 74 G 57 1 98 1 98 1 91 1 87 S 96 1 88 (methyl-) of the carcinogen that was used during its discovery. 66. Soluble GFRa-3 has a MW of approximately 50K. It has one splice variant that is 369 aa in length. The GDNF Receptor family member GFRAL (GDNF Receptor-a-like) has L1CAM NRXN3a LINGO-4 TrkB NT-3 ITGB1 NXPH2 NLGN4X ROBO3 PCDHGB7 MSP R GFRa-4 SynCAM4 LRRTM2 SORT1 PLXNB2 Sema3F Sema6C been shown to be a receptor for GDF-15 and play a putative role in obesity. Neural Cell Adhesion Neurexin 3a LRR and Ig Domain Neurotrophic Tyrosine Neurotrophin 3 Integrin b1 Neurexophilin-2 Neuroligin 4, X-linked Roundabout Homolog 3 Protocadherin gB7 Macrophage Stimulating Glial Cell Line-Derived Synaptic Cell Adhesion Leucine-rich Repeat Sortilin Plexin B2 Semaphorin 3F Semaphorin 6C 67. Carbohydrate moiety regulates SynCAM3 adhesive properties. Molecule L1 C14orf60 Containing Nogo Receptor- Kinase Receptor B NTF3; HDNF; NGF-2 GPIIA; VLA-b; CD29; NPH2 ASPGX2; AUTSX2; HNL4; HNLX; RIG-1; HGPPS; HGPS; RBIG1 Protein Receptor Neurotrophic Factor Molecule 4 Transmembrane Gp95; Neurotensin Receptor 3; MM1; PLEXB2 Sema-IV; SEMA4; SEMAK SEMAY; M-SemaY 68. LRRTM1 is a postsynaptic protein that participates in excitatory synapse formation. The entire molecule is encoded by one exon, and thus, there are no splice variants. CAML1; CD171; HSAS1; Interacting Protein 4 NTRK2; GP145-TrkB FNRB; MDF2; MSK12 NL4 CD136; MST1R; Ron; PTK8 Receptor a4 IGSF4C; CADM4; Necl-4; TSLL2; Neuronal 2 Ntr3; LDLCQ6 69. There are two alternative splice variants, Nogo-B and Nogo-C, which are 373 aa and 199 aa in length, respectively. MASA; MIC5; NgCAM; NCAM-L1; NXPH1, 2, 3; Dystroglycan; BDNF (non-covalent heterodimer); NRXN1a, 2a, 3a NELL2 Ret; PCDHA4 TSLC1-like 2 Sema4A, 4C, 4D, 4G; PLXNA1, A3; NrCAM LRRN6D a b GDNF Ra-4; GFRA4 LRRT2; LRRN2 S10; SPG1 NLGN1, 2, 3 NMDA R; BDNF; NT-3; NT-4; NGF R; TrkB; TrkC; Integrin 9 1; TNC; Integrin a1-a11, aV; Laminin; Fibronectin; NRXN1a, 1b MSP; PLXNB1, B2, B3; Sema4D Neurotensin; ProNGF; ProBDNF; PLXNB1; c-MET; MSP R NRP1, 2; NrCAM 70. PLXNB1 is cleaved to generate a 180K–200K soluble fragment and a 90K–100K membrane-bound fragment. Cleavage occurs between Arg1305 and Val1306, and the two NT-4 (non-covalent heterodimer) LPL; TrkA, B, C; NGF R ligand unknown LINGO-1; SORT1 VCAM-1; TSP; Vitronectin; BGD motif; NGF; PSPN; NCAM-1 SynCAM2, 3; ErbB3; Integrin a6b4 GluR1; NRXN1a, 1b (without an SS4 insert) fragments may remain non-covalently associated. BDNF; NT-3; L1CAM; APP; TNC CNTN1, 2, 5; Integrin b1, b3, b5; NCAM-1 71. Sema3E binds PLXND1 in the absence of NRPs. It is also cleaved into a 60K–61K isoform, which promotes cell migration. * * * * * * * * * * * * * 72. Sema6B is found on neuronal dendrites. 91 190–200K 92 180–190K 93 80–85K 94 135–140K 95 13–14K 96 205–210K 97 26K 98 105–115K 99 125–135K 100 180K 101 50–52K 102 200–330K 103 80–85K 104 60–70K 105 110–125K 106 230–260K 107 100–110K 108 130K 73. L1CAM undergoes cleavage to generate a 35K, 85K and 140K fragment. 1▲ 93 1 93 1 89 1 96 S 91 1 83 S 96 1 60 1 97 1G/S 94 86 S 84 G/ G 89 1 97 1 93 1 84 1 88 1 95 74. The b splice variant of NRXN3 has a MW of 80K–85K, is 668 aa in length, and shows increased binding strength to NLGNs when the SS4 site is present in the molecule. 76. Multiple isoforms of TrkB exist. NrCAM Caspr1 AMIGO TrkC NT-4 ITGB4 NXPH3 NLGN4Y N-Cadherin NCAM-1 EVA1C TNC NgR LRRTM3 NRP1 PLXNB3 Sema4C Sema6D 77. Human NT-3 circulates in the blood at concentrations of 5–10 pg/mL. In contrast, human BDNF circulates in the blood at a concentration of approximately 2000 pg/mL. Neuronal Cell Contactin Associated Amphoterin-Induced Neurotrophic Tyrosine Neurotrophin 4 Integrin b4 Neurexophilin-3 Neuroligin 4, Y-linked Neural Cadherin Neural Cell Adhesion Epithelial V-like Antigen 1 Tenascin C Nogo Receptor Leucine-rich Repeat Neuropilin-1 Plexin B3 Semaphorin 4C Semaphorin 6D 78. ITGB1 is one part of the Integrin a9b1 complex, which binds neurotrophins and promotes cell survival. Adhesion Molecule Protein-like 1 Gene and ORF Kinase Receptor C NT-5; NTF4; NTF5; GLC10 CD104 NPH3 Neuroligin 5 CD325; Cadherin-2; CDH2; CDHN; Molecule-1 Homolog C GMEM; Cytotactin; Hexabrachion f; Nogo-66 Receptor; NgR1; RTN4R; Transmembrane NP1; CD304; VEGF 165 R; BDCA4 PLXN6; PLEXB3; PLEXR Sema-I; SEMAF; M-SEMA-F; 80. NLGN4X is an X-chromosome gene. NLGN4X mutations are associated with impaired synapse formation in autism. NCAD HXB; Tenascin J1; DFNA56 Reticulon 4 Receptor Neuronal 3 SEMACL1 BRAVO CNTN; AP1; p190; NRXN4 Alivin-2; ALI2; AMIGO1 NTRK3; NT-3 Growth Factor CD56; MSK39 FAM176C; SUE21; C21orf63; 81. ROBO3 is thought to also exist as a 1034 aa secreted isoform with a MW of approximately 160K. Receptor; gp145(trkC) TrkB; NGF R; Integrin a6; Laminin; NRXN1a, 2a, 3a NRXN1a C21orf64; PRED34; B18; B19 VEGF 165; Sema3A, 3B, 3C, 3D, 3E, 3F; Sema4G, 5A; PLXNA1, A4; NrCAM Gliomedin; CNTN1, 2; PTPRZ; CNTN1 (in-cis); NFASC AMIGO2, 3 BDNF(non-covalent heterodimer); Netrin-1; SynCAM1, 2, 4 PCDH8; FGF R1 FGF R1; L1CAM; CNTN2; Integrin a9b1; NT-3; BDNF; BMP-2; OMgp; MAG; LINGO-1; TROY; PLXNA1, A2, A3, A4, B1, D1; NRP2; c-MET; MSP R PLXNB1, B2 82. PCDHGB7 is thought to serve as a signaling receptor or subunit for Ret. PCDHGB7 binds to PCDHA4 in-cis. NT-3 (non-covalent heterodimer) b ROBO1; VEGF R2 NFASC; Sema 3F, 6C, 6D NT-3; BDNF; SORT1 BDNF; GFRa-2, -4 Heparin; Slit1, 2 VEGF; TGF- 1; Fibronectin AMIGO3; NGF R; Nogo-A AMPA R complex 83. The MSP R precursor can be cleaved to generate a disulfide-linked heterodimer that consists of a 35K ECD and a 150K transmembrane/cytoplasmic fragment. Although associated with the immune system, MSP is neurotrophic for NGF-responsive pain fibers. The alternate name, Ron, is derived from Recepteur d’Origine Nantais (Receptor “Discovered” in Nantes, France). * * * * * 109 180–190K 110 180K 111 74–78K 112 120–140K 113 210–220K 114 140–150K 115 76–80K 84. GFRa-4 has two splice varients, which are 182 aa and 269 aa in length. The GDNF Receptor family member GFRAL (GDNF Receptor-a-like) has been shown to be a receptor 1 96 1 94 Figure 1. Semaphorin Domain Structure and Receptor Interactions Figure 2. Contactin Domain Structure and Receptor Interactions 1 94 1 95 1 90 1 85 G 89 for GDF-15 and play a putative role in obesity. 85. SynCAM4 is believed to not undergo splicing and is principally expressed by Schwann cells. Domain Key: Notch-1 Domain Key: 87. SORT1 is only active after cleavage of aa 34–77. Additional cleavage generates a 100K soluble isoform. NFASC Caspr2 Sema3A-D, 3F, 3G Sema3E Sema4C Sema4D Sema5A Sema6A Sema7 LRRTM4 NRP2 PLXNC1 Sema4D Sema7A Ig-like APLP-1 APP APLP-1 APP Ig-like Neurofascin Contactin Associated PLXNA2 Leucine-rich Repeat Neuropilin-2 Plexin C1 Semaphorin 4D Semaphorin 7A 88. PLXNB2 is cleaved in the region between Arg1161 and Asp1165, generating a 170K soluble and 80K transmembrane fragment. It is thought that processing of PLXNB2 Sema NFASC NrCAM L1CAM NCAM L1CAM Caspr2 Coagulation Factor V/VIII occurs prior to its interaction with Sema4D. NF; NRCAML Protein-like 2 CNTN2 Transmembrane NP2; NPN2; PRO2714; CD232; VESPR CD100; SEMAJ; M-SEMA-G; BB18; CD108; H-Sema-L; PSI Laminin-like 89. Sema3F binds to NRP1 but exhibits no activity. CNTNAP2; CDFE; NRXN4; cis Neuronal 4 VEGF 165 R2 A8; COLL4; C9orf164 SEMAL; SEMAK1; Gliomedin; NrCAM; Myocilin; AUTS15; PTHSL1 Sema7A JMH Blood Group Antigen 90. Sema6C participates in sensory neuron development; however, in the adult, Sema6C is found only on skeletal muscle fibers. CNTN1; Caspr1 IPT EGF-like 1 LRRT4; LRRN4 VEGF 165; VEGF 145; Sema3C, 3F; PLXNB1, B2; c-MET; PLXNA1, A2; A3, A4, B1; NRP1 ErbB2; MSP R PLXNC1; Integrin a1b1 91. Cleavage of NrCAM generates a 130K–140K a-chain and a 60K-80K b-chain. There are at least 5 splice variants, which have ORFs that are 1174 aa, 1180 aa, 1192 aa, Kv1.1, 1.2; CNTN2 Split GAP Fibrinogen C-terminal AMPA R complex; GPC1–6; NRXN1a, 1b 1236 aa, and 1308 aa in length. Convertase Cleavage Fibronectin Type-III 92. Caspr1 binds to g-secretase and blocks the conversion of Ab to Ab42. Tyrosine Kinase PEST 93. AMIGO serves as a subunit for the Kv2.1 K+ channel. PDZ-Binding Transcriptional Activation Figure 3. GFRa-1 and GFRa-2 Ligand Interactions 94. TrkC has four splice variants that have ORFs that are 612 aa, 817 aa, 831 aa, and 825 aa in length. Basic Nuclear Localization Signal 96. ITGB4 has four splice variants that have ORFs that are 858 aa, 1745 aa, 1752 aa, and 1805 aa in length.
Meprin Ankyrin/CDC10 Repeat 97. ProNXPH3 has a MW of approximately 41K. α GTPase-Binding RAM (GDNF:GFR -1)2: (NCAM-1)2 GDNF2: SYND3 98. NLGN4Y is a Y-chromosome gene whose expression is necessary for synapse formation. There are three splice variants, which are 134 aa, 256 aa, and 648 aa in length. SYND3 Integrin GDNF 100. There are multiple splice variants for NCAM-1 including a “full-length” 180K isoform, a 140K transmembrane short form, a 120K GPI-linked isoform, and a 200-230K poly- NRP2 NrCAM NRP1 PLXND1 c-Met Complement-Binding Lin-Notch Repeat α1β1 SYND3 sialic acid (PSA) modified isoform. Non-PSA-NCAM-1 forms trans-homo-oligomers that mediate both FGF R1 dimerization and GFRa signaling. Coagulation Factor V/VIII EGF Repeat SYND3 c-Met PLXNA3 PLXND1 PLXNB3 PLXNA4 PLXNC1 GDNF : SYND3 102. Human TNC blood concentration is approximately 10–20 ng/mL. There are five splice variants, which are 1655 aa, 1564 aa, 1746 aa, 1837 aa, and 2110 aa in length. VEGF R2 PLXNB2 PLXNB1 Ligand-Binding GPI Anchor NCAM-1 GFRα-1 GFRα-2 2 CNTN1 CNTN2 CNTN5 CNTN3 104. LRRTM3 promotes APP processing by activating BACE1. There is one splice variant that is 513 aa in length. CNTN1 CNTN6 CNTN1 NrCAM CNTN4 CNTN2 Thrombospondin-like GDNF2: SYND3:c-Met Caspr1 α α 105. NRP1 may have both chrondroitin sulfate and heparin sulfate posttranslational modifications. NRP1 homodimers bind to Sema3A. GPI Anchor (GDNF:GFR -1)2 (GDNF:GFR -2)2 106. PLXNB3 does not undergo proteolytic cleavage. PLXNB3-mediated axon guidance is responsible for language development. Ret Ret 108. Sema6D plays a key role in establishing contralateral and ipsilateral connections of the optic nerve. Multiple Sema6D splice variants exist, and proteolysis of the protein generates an 80K fragment. 109. NFASC has multiple splice variants, two of which are NF155 and NF186 (names reflect their respective MWs). NF155 is found on oligodendrocytes while NF186 is expressed α α (GDNF:GFR -1:Ret)2 (GDNF:GFR -2 :Ret)2 in neurons. 110. Caspr2 is thought to be crucial for the proper placement of K+ channels in the nodes of Ranvier. PCDHA4/PCDHGB7 PCDHA4/PCDHGB7 112. NRP2 homodimers bind Sema3F. NRP1:NRP2 heterodimers bind Sema3C. 114. Sema4D is an oligodendrocyte marker. It undergoes proteolysis to generate a circulating 130K bioactive molecule. Sema4D is also reported to use multiple RTKs for cell α α signaling including MSP R and ErbB2/Her2. (GDNF:GFR -1:Ret:PCDHA4/PCDHGB7)2 (GDNF:GFR -2 :Ret:PCDHA4/PCDHGB7)2 115. Sema7A binding to Integrins promotes neuron migration, while Sema7A bonding to PLXNC1 blocks cell migration. NOTE: This poster conveys a general overview and should be considered neither comprehensive nor definitive. The details of this information are understood to be subject to interpretation. © 2014 R&D Systems
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