Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

SARM1 (Sterile Alpha and TIR Motif-Containing Protein 1)

  • Chiung-Ya Chen
  • Yi-Ping Hsueh
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101818

Synonyms

Historical Background

Human sterile alpha and TIR motif-containing protein 1 (SARM1) gene was first cloned and described located at chromosome 17q11 by Mink et al. in 2001. It encodes a protein with domains of sterile alpha motif (SAM) and Armadillo motif (ARM) thus naming SARM (Mink et al. 2001). Later, a Toll/interleukin-1 receptor (TIR) domain was annotated in the C-terminal region of SARM; therefore it was renamed as SARM1 (O’Neill et al. 2003; Mink and Csiszar 2005). TIR domain is present in Toll-like receptors (TLRs), cytokine receptors, and cytoplasm adaptors that mediate innate immune responses to against microbiota infection. There are 10 TLRs in human and 13 TLRs in mice. Those TLRs recognize different components of pathogens and trigger signaling through TIR-TIR domain interactions with distinct TLR adaptors (O’Neill and Bowie 2007). Currently,...

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

References

  1. Carty M, Goodbody R, Schroder M, Stack J, Moynagh PN, Bowie AG. The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling. Nat Immunol. 2006;7:1074–81. doi:10.1038/ni1382.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Chen CY, Lin CW, Chang CY, Jiang ST, Hsueh YP. Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology. J Cell Biol. 2011;193:769–84. doi:10.1083/jcb.201008050.CrossRefPubMedPubMedCentralGoogle Scholar
  3. Chuang CF, Bargmann CI. A Toll-interleukin 1 repeat protein at the synapse specifies asymmetric odorant receptor expression via ASK1 MAPKKK signaling. Genes Dev. 2005;19:270–81. doi:10.1101/gad.1276505.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Coleman MP, Freeman MR. Wallerian degeneration, wld(s), and nmnat. Annu Rev Neurosci. 2010;33:245–67. doi:10.1146/annurev-neuro-060909-153248.CrossRefPubMedPubMedCentralGoogle Scholar
  5. Conforti L, Gilley J, Coleman MP. Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat Rev Neurosci. 2014;15:394–409. doi:10.1038/nrn3680.CrossRefPubMedPubMedCentralGoogle Scholar
  6. Couillault C, Pujol N, Reboul J, Sabatier L, Guichou JF, Kohara Y, et al. TLR-independent control of innate immunity in Caenorhabditis elegans by the TIR domain adaptor protein TIR-1, an ortholog of human SARM. Nat Immunol. 2004;5:488–94. doi:10.1038/ni1060.CrossRefPubMedPubMedCentralGoogle Scholar
  7. Gerdts J, Summers DW, Sasaki Y, DiAntonio A, Milbrandt J. Sarm1-mediated axon degeneration requires both SAM and TIR interactions. J Neurosci. 2013;33:13569–80. doi:10.1523/JNEUROSCI.1197-13.2013.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Kim Y, Zhou P, Qian L, Chuang JZ, Lee J, Li C, et al. MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival. J Exp Med. 2007;204:2063–74. doi:10.1084/jem.20070868.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Liberati NT, Fitzgerald KA, Kim DH, Feinbaum R, Golenbock DT, Ausubel FM. Requirement for a conserved Toll/interleukin-1 resistance domain protein in the Caenorhabditis elegans immune response. Proc Natl Acad Sci U S A. 2004;101:6593–8. doi:10.1073/pnas.0308625101.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Lin CW, Hsueh YP. Sarm1, a neuronal inflammatory regulator, controls social interaction, associative memory and cognitive flexibility in mice. Brain Behav Immun. 2014;37:142–51. doi:10.1016/j.bbi.2013.12.002.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Lin CW, Chen CY, Cheng SJ, Hu HT, Hsueh YP. Sarm1 deficiency impairs synaptic function and leads to behavioral deficits, which can be ameliorated by an mGluR allosteric modulator. Front Cell Neurosci. 2014a;8:87. doi:10.3389/fncel.2014.00087.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Lin CW, Liu HY, Chen CY, Hsueh YP. Neuronally-expressed Sarm1 regulates expression of inflammatory and antiviral cytokines in brains. Innate Immun. 2014b;20:161–72. doi:10.1177/1753425913485877.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Loreto A, Di Stefano M, Gering M, Conforti L. Wallerian degeneration is executed by an NMN-SARM1-dependent late Ca(2+) influx but only modestly influenced by mitochondria. Cell Rep. 2015;13:2539–52. doi:10.1016/j.celrep.2015.11.032.CrossRefPubMedPubMedCentralGoogle Scholar
  14. McLaughlin CN, Nechipurenko IV, Liu N, Broihier HT. A Toll receptor-FoxO pathway represses Pavarotti/MKLP1 to promote microtubule dynamics in motoneurons. J Cell Biol. 2016;214:459–74. doi:10.1083/jcb.201601014.CrossRefPubMedPubMedCentralGoogle Scholar
  15. Mink M, Csiszar K. SARM1: a candidate gene in the onset of hereditary infectious/inflammatory diseases. Clin Immunol. 2005;115:333–4. doi:S1521-6616(05)00069-0.Google Scholar
  16. Mink M, Fogelgren B, Olszewski K, Maroy P, Csiszar K. A novel human gene (SARM) at chromosome 17q11 encodes a protein with a SAM motif and structural similarity to Armadillo/beta-catenin that is conserved in mouse, Drosophila, and Caenorhabditis elegans. Genomics. 2001;74:234–44. doi:10.1006/geno.2001.6548.CrossRefPubMedPubMedCentralGoogle Scholar
  17. O’Neill LA, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007;7:353–64. doi:10.1038/nri2079.CrossRefPubMedPubMedCentralGoogle Scholar
  18. O’Neill LA, Fitzgerald KA, Bowie AG. The Toll-IL-1 receptor adaptor family grows to five members. Trends Immunol. 2003;24:286–90. doi:S1471490603001157.Google Scholar
  19. Osterloh JM, Yang J, Rooney TM, Fox AN, Adalbert R, Powell EH, et al. dSarm/Sarm1 is required for activation of an injury-induced axon death pathway. Science. 2012;337:481–4. doi:10.1126/science.1223899.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Panneerselvam P, Singh LP, Ho B, Chen J, Ding JL. Targeting of pro-apoptotic TLR adaptor SARM to mitochondria: definition of the critical region and residues in the signal sequence. Biochem J. 2012;442:263–71. doi:10.1042/BJ20111653.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Peng J, Yuan Q, Lin B, Panneerselvam P, Wang X, Luan XL, et al. SARM inhibits both TRIF- and MyD88-mediated AP-1 activation. Eur J Immunol. 2010;40:1738–47. doi:10.1002/eji.200940034.CrossRefPubMedPubMedCentralGoogle Scholar
  22. Veriepe J, Fossouo L, Parker JA. Neurodegeneration in C. elegans models of ALS requires TIR-1/Sarm1 immune pathway activation in neurons. Nat Commun. 2015;6:7319. doi:10.1038/ncomms8319.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Yang J, Wu Z, Renier N, Simon DJ, Uryu K, Park DS, et al. Pathological axonal death through a MAPK cascade that triggers a local energy deficit. Cell. 2015;160:161–76. doi:10.1016/j.cell.2014.11.053.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Yuan S, Wu K, Yang M, Xu L, Huang L, Liu H, et al. Amphioxus SARM involved in neural development may function as a suppressor of TLR signaling. J Immunol. 2010;184:6874–81. doi:10.4049/jimmunol.0903675.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Institute of Molecular BiologyTaipeiTaiwan