Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology

Chen, Chiung-Ya; Lin, Chia-Wen; Chang, Chen‐Ming; Jiang, Si‐Tse; Hsueh, Yi‐Ping

doi:10.1083/jcb.201008050

Cited by 122 publications

(144 citation statements)

References 46 publications

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“…The predominantly neuronal expression of Sarm1 distinguishes it from all other TIR domain-containing adaptors involved in TLR signaling [12,14] . Consistent with the original fi nding regarding the involvement of Sarm1 in innate immunity [47] , Sarm1 knockdown in the mouse brain disrupts the expression levels of infl ammatory and antiviral cytokines.…”

Section: Function Of Sarm1 In Brainmentioning

confidence: 99%

“…Using GST-syndecan-2 fusion protein as bait, Sarm1 has been identified as a novel syndecan-2-interacting protein in the mouse brain [12] . Syndecan-2, a synaptic heparan sulfate proteoglycan, regulates synapse formation and dendritic arborization through various downstream mediators [12,52] . For syndecan-2-mediated synapse formation and maintenance, both neurofibromin and CASK protein complexes are required [52][53][54] .…”

Section: Function Of Sarm1 In Brainmentioning

confidence: 99%

“…Sarm1 receives signals from synaptic syndecan-2 and acts through the ASK1-MEK4/7-JNK pathway to modulate dendritic arborization [12] . Interestingly, Sarm1 expression in neurons is detectable far earlier than that of syndecan-2.…”

Section: Function Of Sarm1 In Brainmentioning

confidence: 99%

“…Therefore, Sarm1 also controls syndecan-2-independent events, such as axonal outgrowth and the establishment of neuronal polarity [12] . Thus far, the upstream signal of Sarm1 in regulating axonal outgrowth and neuronal polarity is still unclear.…”

Section: Function Of Sarm1 In Brainmentioning

confidence: 99%

“…In addition to TLRs, neurons also express the critical TIR domain-containing adaptors, which transduce the downstream signals of TLRs, including myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adapter-inducing IFN-β (Trif) [10] and sterile alpha and HEAT/Armadillo motif-containing 1 (Sarm1) [12] . Notably, Sarm1 is predominantly expressed in neurons rather than astrocytes, microglia, or the peripheral immune system [12][13][14] . This characteristic is unique to Sarm1 among all of the known TLRs and TIR domain-containing adaptors.…”

Section: Introductionmentioning

confidence: 99%

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Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

2014

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The central nervous system is recognized as an immunoprivileged site because peripheral immune cells do not typically enter it. Microglial cells are thought to be the main immune cells in brain. However, recent reports have indicated that neurons express the key players of innate immunity, including Toll-like receptors (TLRs) and their adaptor proteins (Sarm1, Myd88, and Trif), and may produce cytokines in response to pathogen infection. In the absence of an immune challenge, neuronal TLRs can detect intrinsic danger signals and modulate neuronal morphology and function. In this article, we review the recent fi ndings on the involvement of TLRs and Sarm1 in controlling neuronal morphogenesis and neurodegeneration. Abnormal behaviors in TLRand Sarm1-defi cient mice are also discussed.

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Section: Function Of Sarm1 In Brainmentioning

confidence: 99%

Section: Function Of Sarm1 In Brainmentioning

confidence: 99%

Section: Function Of Sarm1 In Brainmentioning

confidence: 99%

Section: Function Of Sarm1 In Brainmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

2014

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Asymmetric neural development in the Caenorhabditis elegans olfactory system

Hsieh

Alqadah

Chuang

2014

Genesis

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Asymmetries in the nervous system have been observed throughout the animal kingdom. Deviations of brain asymmetries are associated with a variety of neurodevelopmental disorders; however, there has been limited progress in determining how normal asymmetry is established in vertebrates. In the C. elegans chemosensory system, two pairs of morphologically symmetrical neurons exhibit molecular and functional asymmetries. This review focuses on the development of antisymmetry of the pair of AWC olfactory neurons, from transcriptional regulation of general cell identity, establishment of asymmetry through neural network formation and calcium signaling, to the maintenance of asymmetry throughout the life of the animal. Many of the factors that are involved in AWC development have homologs in vertebrates, which may potentially function in the development of vertebrate brain asymmetry.

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Investigating the role of SARM1 in central nervous system

Wang,

Shi,

Tian

et al. 2024

Ibrain

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Sterile‐α and Toll/interleukin 1 receptor (TIR) motif‐containing protein 1 (SARM1), a key intracellular molecule that plays numerous important biological functions in the nervous system, has attracted much attention. Recent studies have shown that SARM1 plays a key role in nerve injury, degeneration, and neurodegenerative diseases. Therefore, understanding the role of SARM1 in the central nervous system (CNS) will enhance our knowledge of the pathogenesis of CNS diseases and aid in the development of new therapeutic strategies. This review will explore the biological functions of SARM1 in the nervous system and its potential roles in nerve injury and disease, thus providing new directions for future research and treatment.

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Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology

Abstract: The syndecan Sds2 and the innate immunity inhibitor Sarm1 function together and in distinct pathways to promote proper neuronal morphogenesis.

Cited by 122 publications

References 46 publications

Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

Innate immune responses regulate morphogenesis and degeneration: roles of Toll-like receptors and Sarm1 in neurons

Asymmetric neural development in the Caenorhabditis elegans olfactory system

Investigating the role of SARM1 in central nervous system

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