Biology subjects

Capuana, L.

Publications and source records attributed to Capuana, L..

2 recordsLinked to original sources

bioRxiv2022

Trim33 conditions the lifespan of primitive macrophages and onset of definitive macrophage production

TRIM33 (Tif1-{gamma}) is a transcriptional regulator notably involved in several aspects of hematopoiesis. It is essential for the production of erythrocytes in zebrafish, and for the proper functionning and aging of hematopoietic stem and progenitor cells (HSPCs) in mice. Here we have found that in zebrafish development, Trim33 is essential cell-autonomously for the lifespan of the yolk sac derived primitive macrophages, as well as for the initial production of definitive (HSPC-derived) macrophages in the first niche of definitive hematopoiesis, the caudal hematopoietic tissue. Moreover, Trim33 deficiency leads to an excess production of definitive neutrophils and thrombocytes. Our data indicate that Trim33 radically conditions the differentiation ouput of aorta-derived HSPCs in all four erythro-myeloid cell types, in a niche-specific manner.

developmental biology↗

bioRxiv2021

PTEN inhibits AMPK to control collective migration

PTEN is one of the most frequently mutated tumor suppressor gene in cancer. PTEN is generally altered in invasive cancers such as glioblastomas, but its function in collective cell migration and invasion is not fully characterized. Herein, we report that the loss of PTEN increases cell speed during collective migration of non-tumourous cells both in vitro and in vivo. We further show that loss of PTEN promotes LKB1-dependent phosphorylation and activation of the major metabolic regulator AMPK. In turn AMPK increases VASP phosphorylation, reduces VASP localization at cell-cell junctions and decreases the interjunctional transverse actin arcs at the leading front, provoking a weakening of cell-cell contacts and increasing migration speed. Targeting AMPK activity not only slows down PTEN-depleted cells, it also limits PTEN-null glioblastoma cell invasion, opening new opportunities to treat glioblastoma lethal invasiveness.

cell biology↗