The cationic amino acid exporter Slc7a7 is induced and vital in zebrafish tissue macrophages with sustained efferocytic activity.
Doris Lou DemyMireille CarrèreRamil NocheMuriel TauzinMarion Le BrisChooyoung BaekIgnaty LeshchinerWolfram GoesslingPhilippe HerbomelPublished in: Journal of cell science (2020)
Most tissues harbor a substantial population of resident macrophages. Here, we elucidate a functional link between the Slc7a7 cationic amino acid transporter and tissue macrophages. We identified a mutant zebrafish devoid of microglia due to a mutation in the slc7a7 gene. We found that in Slc7a7-deficient larvae, macrophages do enter the retina and brain to become microglia, but then die during the developmental wave of neuronal apoptosis, which triggers intense efferocytic work from them. A similar macrophage demise occurs in other tissues, at stages where macrophages have to engulf many cell corpses, whether due to developmental or experimentally triggered cell death. We found that Slc7a7 is the main cationic amino acid transporter expressed in macrophages of zebrafish larvae, and that its expression is induced in tissue macrophages within 1-2 h upon efferocytosis. Our data indicate that Slc7a7 is vital not only for microglia but also for any steadily efferocytic tissue macrophages, and that slc7a7 gene induction is one of the adaptive responses that allow them to cope with the catabolism of numerous dead cells without compromising their own viability.
Keyphrases
- amino acid
- cell death
- cell cycle arrest
- inflammatory response
- gene expression
- adipose tissue
- machine learning
- multiple sclerosis
- high glucose
- spinal cord injury
- neuropathic pain
- single cell
- diabetic rats
- stem cells
- drug induced
- endoplasmic reticulum stress
- patient safety
- signaling pathway
- artificial intelligence
- brain injury
- wild type
- spinal cord
- diabetic retinopathy
- stress induced