Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

Cbln1

  • Keiko Matsuda
  • Michisuke Yuzaki
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_643

Synonyms

Historical Background

In 1984, the cerebellum-specific hexadecapeptide “cerebellin” was identified and shown to be concentrated in the synaptosomal compartment (Slemmon et al. 1984). Although “precerebellin” was originally identified as a precursor of cerebellin, the cerebellin peptide is not flanked by the classical dibasic amino acids observed in many neuropeptide precursors (Urade et al. 1991). In addition, precerebellin clearly belongs to the C1q family, whose members, such as C1q, adiponectin (Adipoq), and collagen X, are secreted and are involved in various intercellular functions (Yuzaki 2008). Indeed, full-length, uncleaved precerebellin is secreted from cerebellar granule cells (Bao et al. 2005; Iijima et al. 2007). Therefore, it is now evident that precerebellin is the actual signaling molecule itself, which should be referred to as Cbln1, although the cerebellin peptide may have additional functions.

Basic Features

Cbln1 is predominantly expressed in...

This is a preview of subscription content, log in to check access.

References

  1. Bao D, Pang Z, Morgan JI. The structure and proteolytic processing of Cbln1 complexes. J Neurochem. 2005;95:618–29.PubMedCrossRefGoogle Scholar
  2. Bolliger MF, Martinelli DC, Sudhof TC. The cell-adhesion G protein-coupled receptor BAI3 is a high-affinity receptor for C1q-like proteins. Proc Natl Acad Sci USA. 2011;108:2534–9.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Cagle MC, Honig MG. Parcellation of cerebellins 1, 2, and 4 among different subpopulations of dorsal horn neurons in mouse spinal cord. J Comp Neurol. 2014;522:479–97.PubMedCrossRefGoogle Scholar
  4. Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR. Structural basis for integration of GluD receptors within synaptic organizer complexes. Science. 2016;353:295–9.PubMedPubMedCentralCrossRefGoogle Scholar
  5. Fox MA, Umemori H. Seeking long-term relationship: axon and target communicate to organize synaptic differentiation. J Neurochem. 2006;97:1215–31.PubMedCrossRefGoogle Scholar
  6. Fukata Y, Lovero KL, Iwanaga T, Watanabe A, Yokoi N, Tabuchi K, et al. Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. Proc Natl Acad Sci USA. 2010;107:3799–804.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Hirai H, Pang Z, Bao D, Miyazaki T, Li L, Miura E, et al. Cbln1 is essential for synaptic integrity and plasticity in the cerebellum. Nat Neurosci. 2005;8:1534–41.PubMedCrossRefGoogle Scholar
  8. Iijima T, Miura E, Matsuda K, Kamekawa Y, Watanabe M, Yuzaki M. Characterization of a transneuronal cytokine family Cbln–regulation of secretion by heteromeric assembly. Eur J Neurosci. 2007;25:1049–57.PubMedCrossRefGoogle Scholar
  9. Ito-Ishida A, Miura E, Emi K, Matsuda K, Iijima T, Kondo T, et al. Cbln1 regulates rapid formation and maintenance of excitatory synapses in mature cerebellar Purkinje cells in vitro and in vivo. J Neurosci. 2008;28:5920–30.PubMedCrossRefGoogle Scholar
  10. Ito-Ishida A, Miyazaki T, Miura E, Matsuda K, Watanabe M, Yuzaki M, Okabe S. Presynaptically released Cbln1 induces dynamic axonal structural changes by interacting with GluD2 during cerebellar synapse formation. Neuron. 2012;76:549–64.PubMedCrossRefGoogle Scholar
  11. Kakegawa W, Mitakidis N, Miura E, Abe M, Matsuda K, Takeo YH, Kohda K, Motohashi J, Takahashi A, Nagao S, Muramatsu S, Watanabe M, Sakimura K, Aricescu AR, Yuzaki M. Anterograde C1ql1 signaling is required in order to determine and maintain a single-winner climbing fiber in the mouse cerebellum. Neuron. 2015;85:316–29.PubMedPubMedCentralCrossRefGoogle Scholar
  12. Konno K, Matsuda K, Nakamoto C, Uchigashima M, Miyazaki T, Yamasaki M, Sakimura K, Yuzaki M, Watanabe M. Enriched expression of GluD1 in higher brain regions and its involvement in parallel fiber-interneuron synapse formation in the cerebellum. J Neurosci. 2014;34:7412–24.PubMedCrossRefGoogle Scholar
  13. Ledda F, Paratcha G, Sandoval-Guzman T, Ibanez CF. GDNF and GFRalpha1 promote formation of neuronal synapses by ligand-induced cell adhesion. Nat Neurosci. 2007;10:293–300.PubMedCrossRefGoogle Scholar
  14. Matsuda K, Yuzaki M. Cbln family proteins promote synapse formation by regulating distinct neurexin signaling pathways in various brain regions. Eur J Neurosci. 2011;33:1447–61.PubMedCrossRefGoogle Scholar
  15. Matsuda K, Miura E, Miyazaki T, Kakegawa W, Emi K, Narumi S, et al. Cbln1 is a ligand for an orphan glutamate receptor delta2, a bidirectional synapse organizer. Science. 2010;328:363–8.PubMedCrossRefGoogle Scholar
  16. Matsuda K, Budisantoso T, Mitakidis N, Sugaya Y, Miura E, Kakegawa W, Yamasaki M, Konno K, Uchigashima M, Abe M, Watanabe I, Kano M, Watanabe M, Sakimura K, Aricescu AR, Yuzaki M. Transsynaptic modulation of kainate receptor functions by C1q-like Proteins. Neuron. 2016;90:752–67.PubMedCrossRefGoogle Scholar
  17. Miura E, Iijima T, Yuzaki M, Watanabe M. Distinct expression of Cbln family mRNAs in developing and adult mouse brains. Eur J Neurosci. 2006;24:750–60.PubMedCrossRefGoogle Scholar
  18. Otsuka S, Konno K, Abe M, Motohashi J, Kohda K, Sakimura K, Watanabe M, Yuzaki M. Roles of Cbln1 in non-motor functions of mice. J Neurosci. 2016; 36:11801–16.PubMedCrossRefGoogle Scholar
  19. Ryu K, Yokoyama M, Yamashita M, Hirano T. Induction of excitatory and inhibitory presynaptic differentiation by GluD1. Biochem Biophys Res Commun. 2012;417:157–61.PubMedCrossRefGoogle Scholar
  20. Slemmon JR, Blacher R, Danho W, Hempstead JL, Morgan JI. Isolation and sequencing of two cerebellum-specific peptides. Proc Natl Acad Sci USA. 1984;81:6866–70.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Stevens B, Allen NJ, Vazquez LE, Howell GR, Christopherson KS, Nouri N, et al. The classical complement cascade mediates CNS synapse elimination. Cell. 2007;131:1164–78.PubMedCrossRefGoogle Scholar
  22. Uemura T, Lee SJ, Yasumura M, Takeuchi T, Yoshida T, Ra M, et al. Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum. Cell. 2010;141:1068–79.PubMedCrossRefGoogle Scholar
  23. Urade Y, Oberdick J, Molinar-Rode R, Morgan JI. Precerebellin is a cerebellum-specific protein with similarity to the globular domain of complement C1q B chain. Proc Natl Acad Sci USA. 1991;88:1069–73.PubMedPubMedCentralCrossRefGoogle Scholar
  24. Wei P, Pattarini R, Rong Y, Guo H, Bansal PK, Kusnoor SV, Deutch AY, Parris J, Morgan JI. The Cbln family of proteins interact with multiple signaling pathways. J Neurochem. 2012;121:717–29.PubMedPubMedCentralCrossRefGoogle Scholar
  25. Yang M, Cagle MC, Honig MG. Identification of cerebellin2 in chick and its preferential expression by subsets of developing sensory neurons and their targets in the dorsal horn. J Comp Neurol. 2010;518:2818–40.PubMedPubMedCentralGoogle Scholar
  26. Yasumura M, Yoshida T, Lee SJ, Uemura T, Joo JY, Mishina M. Glutamate receptor delta1 induces preferentially inhibitory presynaptic differentiation of cortical neurons by interacting with neurexins through cerebellin precursor protein subtypes. J Neurochem. 2012;121:705–16.PubMedCrossRefGoogle Scholar
  27. Yuzaki M. Cbln and C1q family proteins: new transneuronal cytokines. Cell Mol Life Sci. 2008;65:1698–705.PubMedCrossRefGoogle Scholar
  28. Yuzaki M. New (but old) molecules regulating synapse integrity and plasticity: Cbln1 and the delta2 glutamate receptor. Neuroscience. 2009;162:633–43.PubMedCrossRefGoogle Scholar
  29. Yuzaki M. Cbln1 and its family proteins in synapse formation and maintenance. Curr Opin Neurobiol. 2011;21:215–20.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of PhysiologyKeio University School of MedicineTokyoJapan
  2. 2.Department of NeurophysiologySchool of Medicine, Keio UniversityShinjuku-ku, TokyoJapan