Beyond TLR Signaling—The Role of SARM in Antiviral Immune Defense, Apoptosis & Development.
SARM (Sterile alpha and armadillo motif-containing protein) is the recently identified TIR domain-containing cytosolic protein. Classified as a member of the TLR adaptor family, the multiple locations and functions of SARM (sometimes playing opposing roles), provoke an enigma on its biology. Although originally assumed to be a member of the TLR adaptor family (functioning as a negative regulator of TLR signaling pathway), latest findings indicate that SARM regulates signaling differently from other TLR adaptor proteins. Recent studies have highlighted the significant functional role of SARM in mediating apoptosis and antiviral innate immune response. In this review, we provide an update on the evolutionary conservation, spatial distribution, and regulated expression of SARM to highlight its diverse functional roles. The review will summarize findings on the known interacting partners of SARM and provide analogy on how they add new dimensions to the current understanding on the multifaceted roles of SARM in antiviral activities and apoptotic functions. In addition, we provide a future perspective on the roles of SARM in differentiation and development, with substantial emphasis on the molecular insights to its mechanisms of action.
a Department of Biological Sciences , National University of Singapore , Singapore.|b Computational and Systems Biology , Singapore-MIT Alliance , Singapore.
Porkodi
P
Panneerselvam
a Department of Biological Sciences , National University of Singapore , Singapore.|b Computational and Systems Biology , Singapore-MIT Alliance , Singapore.
Jeak Ling
JL
Ding
D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D051186:Armadillo Domain Proteins / Q000276:immunology*; D003598:Cytoskeletal Proteins / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000276:immunology*; D014780:Viruses / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins; C435689:SARM1 protein, human; D051193:Toll-Like Receptors
TLR adaptors; TLR signaling pathways; antiviral; apoptosis; cell death; innate immunity