Prominin‐like, a homolog of mammalian CD133, suppresses dilp6and TOR signaling to maintain body size and weight inDrosophila

What is it about?

Drosophila prominin-like is a homologous gene of mammalian CD133 (also known as AC133/Prominin-1). CD133 has been used as a molecular marker for putative cancer stem cells in various tumors. Following the recognition of its intriguing involvement in defining stem cells/progenitors, CD133 has been investigated in animal models such as Drosophila, Xenopus laevis and rodents where it shows conserved cellular roles in invertebrate and vertebrate photoreceptor cells. In Drosophila, the physiological properties of homolog of CD133, prominin-like is less understood and the genetic mutant of Prominin-like has not been previously constructed. We have generated genetic mutants of prominin-like. Prominin-like mutants survive to the adulthood and exhibit a larger body size and excessive weight accompanied with higher fat deposits. Increased dilp6 transcriptional levels are observed in these mutants during the wandering third instar larvae stage or upon starvation. Akt/dTOR signaling is also up-regulated in the adult mutants. On an amino-acid-restricted diet, Prominin-like mutants exhibit an extremely larger size than the wild type, similar to when the dTOR pathway is activated in the fat body. We show that Prominin-like negatively regulates the dTOR pathway and dilp6 levels influencing the control of body size and body weight and the associated aspects of fat storage in adults. Ectopic expression of CD133 causes a similar decreased body size as overexpression of Prominin-like. The identification of the physiological function of Prominin-like in an in vivo animal model may provide insight into the metabolic function of CD133 in mammals.

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