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Merck
  • The cationic amino acid exporter Slc7a7 is induced and vital in zebrafish tissue macrophages with sustained efferocytic activity.

The cationic amino acid exporter Slc7a7 is induced and vital in zebrafish tissue macrophages with sustained efferocytic activity.

Journal of cell science (2020-09-26)
Doris Lou Demy, Mireille Carrère, Ramil Noche, Muriel Tauzin, Marion Le Bris, Chooyoung Baek, Ignaty Leshchiner, Wolfram Goessling, Philippe Herbomel
초록

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.

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Sigma-Aldrich
Neutral Red, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
N-Phenylthiourea, ≥98%
Supelco
Ethyl 3-aminobenzoate methanesulfonate salt, analytical standard
Sigma-Aldrich
Phenylhydrazine, 97%
Sigma-Aldrich
Methylene Blue hydrate, suitable for nucleic acid staining, BioReagent