TAFA4 relieves injury-induced mechanical hypersensitivity through LDL receptors and modulation of spinal A-type K+ current

Yoo, Seung‐Hyun; Santos, Catarina; Reynders, Ana; Marics, Irène; Malapert, Pascale; Gaillard, Stéphane; Charron, Aude; Ugolini, Sophie; Rossignol, Rafaëlle; Khallouqi, Abderazzak El; Springael, Jean–Yves; Parmentier, Marc; Saurin, Andrew J.; Goaillard, Jean-Marc; Castets, Francis; Clerc, Nadine; Moqrich, Aziz

doi:10.1016/j.celrep.2021.109884

Cited by 15 publications

(15 citation statements)

References 46 publications

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Section: The Roles Of Tafa4 and Fpr1 In The Spinal Cordmentioning

confidence: 98%

“…Most recently, TAFA4 was shown to relieve injury-induced mechanical hypersensitivity by restoring spinal neuron activity to normal, which is further suggestive of its therapeutic potential ( Yoo et al, 2021 ). TAFA 4 was found to reverse inflammatory, postoperative, and spared nerve injury (SNI)-induced mechanical pain in mice ( Yoo et al, 2021 ). Mechanistically TAFA4 was able to reverse injury-induced A-type K + (I A ) current decreases in spinal lamina II outer excitatory interneurons (L-IIo ExINs) and was also able to simultaneously reverse SNI-induced increases in I A and decreases in hyperpolarization-activated current (I h ) in lamina II inner inhibitory interneurons (L-IIi InhINs) ( Yoo et al, 2021 ).…”

Section: The Roles Of Tafa4 and Fpr1 In The Spinal Cordmentioning

confidence: 98%

“…TAFA 4 was found to reverse inflammatory, postoperative, and spared nerve injury (SNI)-induced mechanical pain in mice ( Yoo et al, 2021 ). Mechanistically TAFA4 was able to reverse injury-induced A-type K + (I A ) current decreases in spinal lamina II outer excitatory interneurons (L-IIo ExINs) and was also able to simultaneously reverse SNI-induced increases in I A and decreases in hyperpolarization-activated current (I h ) in lamina II inner inhibitory interneurons (L-IIi InhINs) ( Yoo et al, 2021 ). The rescue of ion current changes to normal levels in both IN groups was dependent on low-density lipoprotein receptor-related proteins (LRPs) ( Yoo et al, 2021 ).…”

Section: The Roles Of Tafa4 and Fpr1 In The Spinal Cordmentioning

confidence: 99%

“…Mechanistically TAFA4 was able to reverse injury-induced A-type K + (I A ) current decreases in spinal lamina II outer excitatory interneurons (L-IIo ExINs) and was also able to simultaneously reverse SNI-induced increases in I A and decreases in hyperpolarization-activated current (I h ) in lamina II inner inhibitory interneurons (L-IIi InhINs) ( Yoo et al, 2021 ). The rescue of ion current changes to normal levels in both IN groups was dependent on low-density lipoprotein receptor-related proteins (LRPs) ( Yoo et al, 2021 ). TAFA4 therefore is effective at reversing injury-induced mechanical hypersensitivity and is a prime therapeutic target for the treatment of injury-induced mechanical pain.…”

Section: The Roles Of Tafa4 and Fpr1 In The Spinal Cordmentioning

confidence: 99%

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Molecular Structure, Expression and Role of TAFA4 and its Receptor FPR1 in the Spinal Cord

Zhu

Bennett

et al. 2022

Front. Cell Dev. Biol.

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TAFA chemokine like family member 4 (TAFA4, also named FAM19A4) is a member of the TAFA chemokine like ligand or FAM19A family, which includes TAFA1, TAFA2, TAFA3, TAFA4, and TAFA5 (or FAM19A1, FAM19A2, FAM19A3, FAM19A4, and FAM19A5). They are also referred to as neurokines and are involved in the regulation of a diverse range of cellular processes, including chemotaxis of macrophages, phagocytosis, and release of reactive oxygen species (ROS). TAFA4 is a marker of C-low-threshold mechanoreceptors and is expressed predominantly in nociceptors, such as dorsal root ganglia (DRG). TAFA4 has been implicated in the sensory perception of pain in the spinal cord. Mice with deficiency of TAFA4 demonstrate altered excitability in lamina IIi neurons in DRG in addition to increased mechanical and chemical nociception following inflammation or injury. As a secreted protein, TAFA4 binds to cell surface receptor formyl peptide receptor 1 (FPR1), a G protein-coupled receptor to mediate the chemoattraction of macrophages, phagocytosis, and the inflammatory profile of macrophages. It also interacts with cell surface neurexin to mediate signalling across the synapse. Further understanding the mechanisms by which this conserved protein family regulates diverse biological processes such as in neuronal functions, inflammation, and tissue fibrosis will help to design therapeutic targets for the treatment of TAFA related diseases such as spinal cord injury and neuro-inflammatory disorders.

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Section: The Roles Of Tafa4 and Fpr1 In The Spinal Cordmentioning

confidence: 98%

Section: The Roles Of Tafa4 and Fpr1 In The Spinal Cordmentioning

confidence: 98%

Section: The Roles Of Tafa4 and Fpr1 In The Spinal Cordmentioning

confidence: 99%

Section: The Roles Of Tafa4 and Fpr1 In The Spinal Cordmentioning

confidence: 99%

See 2 more Smart Citations

Molecular Structure, Expression and Role of TAFA4 and its Receptor FPR1 in the Spinal Cord

Zhu

Bennett

et al. 2022

Front. Cell Dev. Biol.

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“…Numerous studies have highlighted the therapeutic potential for targeting the neuro-immune axis [22][23][24][25][26][27][28][29][30] . For example, Hoeffel et.…”

Section: Introductionmentioning

confidence: 99%

High-resolution cross-species transcriptomic atlas of dorsal root ganglia reveals species-specific programs for sensory function

Jung¹,

Dourado²,

Maksymetz³

et al. 2022

Preprint

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Sensory neurons of the dorsal root ganglion (DRG) play a crucial role in maintaining tissue homeostasis by sensing and initiating responses to stimuli. While most preclinical studies of DRGs are conducted in rodents, much less is known about the mechanisms of sensory perception in primates. We generated a transcriptome atlas of mouse, guinea pig, cynomolgus monkey, and human DRGs using a framework that implements a common laboratory workflow and multiple data-integration approaches to generate high-resolution cross-species mappings of sensory neuron subtypes. Using our atlas, we identified conserved core modules highlighting subtype-specific biological processes related to inflammatory response. We also identified divergent expression of key genes involved in DRG function, suggesting species-specific adaptations. Among these, we validated that Tafa4, a member of the druggable genome, was expressed in distinct populations of DRG neurons across species, highlighting species-specific programs that are critical for therapeutic development.

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Diverse roles and modulations of IA in spinal cord pain circuits

Clerc

Moqrich

2022

Cell Reports

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TAFA4 relieves injury-induced mechanical hypersensitivity through LDL receptors and modulation of spinal A-type K+ current

Cited by 15 publications

References 46 publications

Molecular Structure, Expression and Role of TAFA4 and its Receptor FPR1 in the Spinal Cord

Molecular Structure, Expression and Role of TAFA4 and its Receptor FPR1 in the Spinal Cord

High-resolution cross-species transcriptomic atlas of dorsal root ganglia reveals species-specific programs for sensory function

Diverse roles and modulations of IA in spinal cord pain circuits

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