Abstract:
: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.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Demy DL,Carrère M,Noche R,Tauzin M,Le Bris M,Baek C,Leshchiner I,Goessling W,Herbomel Pdoi
10.1242/jcs.249037subject
Has Abstractpub_date
2020-10-22 00:00:00issue
20eissn
0021-9533issn
1477-9137pii
jcs.249037journal_volume
133pub_type
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