Gtdap-1 promotes autophagy and is required for planarian remodeling during regeneration and starvation

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Abstract
Remodeling is an integral component of tissue homeostasis and regeneration. In planarians, these processes occur constantly in a simple tractable model organism as part of the animal's normal life history. Here, we have studied the gene Gtdap-1, the planarian ortholog of human death-associated protein-1 or DAP-1. DAP-1, together with DAP-kinase, has been identified as a positive mediator of programmed cell death induced by gamma-IFN in HeLa cells. Although the function of DAP-kinase is well characterized, the role of DAP-1 has not been studied in detail. Our findings suggest that Gtdap-1 is involved in autophagy in planarians, and that autophagy plays an essential role in the remodeling of the organism that occurs during regeneration and starvation, providing the necessary energy and building blocks to the neoblasts for cell proliferation and differentiation. The gene functions at the interface between survival and cell death during stress-inducing processes like regeneration and starvation in sexual and asexual races of planarians. Our findings provide insights into the complex interconnections among cell proliferation, homeostasis, and cell death in planarians and perspectives for the understanding of neoblast stem cell dynamics.