PerspectiveCell Biology

Studies of SARM1 Uncover Similarities Between Immune and Neuronal Responses to Danger

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Science's STKE  18 Dec 2007:
Vol. 2007, Issue 417, pp. pe73
DOI: 10.1126/stke.4172007pe73

Figures

  • Fig. 1.

    Potential roles for SARM1 in mammalian immune responses to danger. Among human and mouse leukocytes, SARM1 is selectively found in lymphocytes, especially in CD8+ T cells. SARM1 may shape CD8+ T cell responses to the activation of TLR3 (not shown in the figure) or TLR4 by inhibiting the canonical TRIF-dependent pathway that leads to NF-κB activation and by promoting the use of an alternative ASK1-MAPK cascade, which leads to the recruitment of p38 and JNK. TIR domains in the relevant proteins are represented by circles; SAM domains in SARM1 are represented by hexagons. ZAP, T cell receptor zeta-chain–associated protein kinase; IRAK, interleukin-1 receptor–associated kinase; TRAF, tumor necrosis factor receptor–associated factor; MKK4, -6, and -7, mitogen-activated protein kinase kinases; NFAT, nuclear factor of activated T cells.

  • Fig. 2.

    Modeling the role of SARM1 in the tuning of mammalian neuronal responses to danger. SARM1 is highly abundant in neurons, where it is associated with mitochondria and recruits JNK3 to induce apoptosis upon metabolic stress. The transduction cascade downstream of JNK3 in this pathway remains to be deciphered but may include translocation of the proapoptotic molecule Bax to mitochondria, which results in the triggering of apoptosis. In C. elegans, the MAP kinase NSY-1 binds to TIR-1, the ortholog of SARM1, and mediates downstream signaling for both immune function and neuronal development. In mammals, the ortholog of NSY-1, ASK1, is also involved in neuronal apoptosis upon metabolic stress. TIR domains in the relevant proteins are represented by circles; SAM domains in SARM1 are represented by hexagons. IRF, interferon regulatory factor.

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