The neuronal genome of Caenorhabditis elegans* Oliver Hobert§ Columbia University Medical Center, HHMI, New York, NY, USA Table of Contents 1. Introduction ............................................................................................................................3 2. Ion channels ...........................................................................................................................6 2.1. Potassium channels ........................................................................................................ 8 2.2. Calcium channels, transporters and calcium binding proteins ................................................. 9 2.3. TRP channels ............................................................................................................. 12 2.4. Cyclic nucleotide-gated ion channels .............................................................................. 12 2.5. Ligand-gated ion channels ............................................................................................ 12 2.6. Ionotropic glutamate receptors ....................................................................................... 15 2.7. DEG/ENaC/ASIC channels ........................................................................................... 15 2.8. Chloride channels and chloride transporters ...................................................................... 16 2.9. New ion channels ........................................................................................................ 17 2.10. Summary of absent ion channels ................................................................................... 18 3. Neurotransmitter pathways ...................................................................................................... 18 3.1. Neurotransmitter synthesis ............................................................................................ 19 3.2. Vesicular transport of neurotransmitters ........................................................................... 21 3.3. Neurotransmitter reuptake ............................................................................................. 22 3.4. Neurotransmitter degradation ........................................................................................ 23 3.5. The case for and against other neurotransmitter systems ..................................................... 23 4. Neuropeptides ....................................................................................................................... 25 4.1. Neuropeptide-encoding genes ........................................................................................ 25 4.2. Biosynthesis and processing of neuropeptides ................................................................... 25 4.3. Neuropeptide receptors ................................................................................................. 26 5. G-protein coupled receptors (GPCRs) ........................................................................................ 26 5.1. Metabotropic neurotransmitter receptors .......................................................................... 27 5.2. Neuropeptide receptors ................................................................................................. 27 5.3. Sensory and orphan receptors ........................................................................................ 28 5.4. Adhesion GPCRs ........................................................................................................ 29 5.5. Frizzled/Taste2 GPCRs ................................................................................................ 29 *Edited by: Eric Jorgensen. Last revised December 27, 2012, Published August 13, 2013. This chapter should be cited as: Hobert O. The neuronal genome of Caenorhabditis elegans (August 13, 2013), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.161.1, http://www.wormbook.org. Copyright: © 2013 Oliver Hobert. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. §To whom correspondence should be addressed: E-mail [email protected] 1 The neuronal genome of Caenorhabditis elegans 5.6. Downstream of GPCRs ................................................................................................ 29 6. Cyclic GMP .......................................................................................................................... 30 6.1. Guanylyl cyclases ....................................................................................................... 30 6.2. Phosphodiesterases ...................................................................................................... 31 7. Receptors for CO and O ........................................................................................................ 31 2 2 8. Presynaptic machinery ............................................................................................................ 31 9. Neurotransmitter receptor localization: PDZ proteins .................................................................... 32 10. Gap junctions - the innexins ................................................................................................... 32 11. Motor proteins & their associated complexes ............................................................................. 33 11.1. Kinesin, dynein and myosin motors ............................................................................... 33 11.2. Motor complexes that build cilia of sensory neurons ......................................................... 33 12. Neuronal recognition and adhesion molecules ............................................................................ 33 12.1. Immunoglobulin superfamily ....................................................................................... 34 12.2. Leucine-Rich Repeat (LRR) proteins ............................................................................. 34 12.3. Cadherins ................................................................................................................. 34 12.4. Neurexin and its ligands .............................................................................................. 35 13. Conclusions ........................................................................................................................ 35 14. Tables 2-35 ......................................................................................................................... 36 Table 2: Potassium channels (72 genes) ................................................................................. 36 Table 3: Candidate auxiliary subunits for various types of ion channels (93 genes) ........................ 39 Table 4: Voltage-gated calcium channels (9 genes) .................................................................. 42 Table 5: SLC transporters with confirmed or putative neuronal functions (82 genes) ...................... 43 Table 6: Calcium binding proteins – the “EF hand-only” proteins (65 genes) ................................ 46 Table 7: TRP channels (23 genes) ........................................................................................ 48 Table 8: Cyclic nucleotide gated channels (6 genes) ................................................................. 49 Table 9: nAChR-type ligand-gated ion channels of the Cys-loop LGIC superfamily (61 genes) ........ 50 Table 10: Other ligand-gated ion channels of the Cys-loop LGIC superfamily (41 genes) ................ 52 Table 11: Ionotropic glutamate receptors (15 genes) ................................................................ 53 Table 12: DEG/ENaC channels (32 genes) ............................................................................. 54 Table 13: Chloride channels (35 genes) ................................................................................. 55 Table 14: Neurotransmitter synthesis and degradation (36 genes) ............................................... 56 Table 15: Neuropeptide-encoding genes (122 genes) ................................................................ 58 Table 16: Metabolism of neuropeptides (47 genes) .................................................................. 59 Table 17: Insulin/EGF receptor-like proteins (70 genes) ........................................................... 61 Table 18: The five classes of GPCRs .................................................................................... 63 Table 19: Metabotropic neurotransmitter receptors (27 genes) ................................................... 64 Table 20: GPCR-type putative neuropeptide receptors and their grouping into families (153 genes) .. 65 Table 21: Representative analysis of srw genes reveals their relation to neuropeptide receptors ........ 73 Table 22: Adhesion-type GPCRs (5 genes) ............................................................................. 74 Table 23: Downstream of GPCRs (83 genes) .......................................................................... 75 Table 24: Making and breaking cGMP - Guanylyl cyclases and phosphodiesterases (40 genes) ........ 77 Table 25: Receptors of CO and O (39 genes plus 7 soluble GCY genes) .................................... 78 2 2 Table 26: Synaptic vesicle proteins and their homologs (57 genes)