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Periodic Table of Neurotrophic and Neurotactic Factors

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Periodic Table of Neurotrophic and Neurotactic Factors 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. 3. CNTN2 mutations are associated with epilepsy. G/ G 95 1 90 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. 25. NGF R may be cleaved to generate a 20K and 25K intracellular domain fragment that exhibit growth arrest activity. G/ G 91 1 89 1 93 S▲ 94 S 86 1 97 S 95 1▲ 93 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 fragment binds to GPC1. Slit2 has two splice variants, which are 1521 aa and 1525 aa in length. 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 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.
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