Year-end Sale % OFF 
Abstract
BackgroundAkt (PKB) is a serine threonine protein kinase downstream of the phosphoinositide 3-kinase (PI3K) pathway. In mammals, Akt is ubiquitously expressed and is associated with regulation of cellular proliferation, metabolism, cell growth and cell death. Akt has been widely studied for its central role in physiology and disease, in particular cancer where it has become an attractive pharmacological target. However, the mechanisms by which Akt signaling regulates stem cell behavior in the complexity of the whole body are poorly understood. Planarians are flatworms with large populations of stem cells capable of dividing to support adult tissue renewal and regeneration. The planarian ortholog Smed-Akt is molecularly conserved providing unique opportunities to analyze the function of Akt during cellular turnover and repair of adult tissues.ResultsOur findings abrogating Smed-Akt with RNA-interference in the planarian Schmidtea mediterranea led to a gradual decrease in stem cell (neoblasts) numbers. The reduced neoblast numbers largely affected the maintenance of adult tissues including the nervous and excretory systems and ciliated structures in the ventral epithelia, which impaired planarian locomotion. Downregulation of Smed-Akt function also resulted in an increase of cell death throughout the animal. However, in response to amputation, levels of cell death were decreased and failed to localize near the injury site. Interestingly, the neoblast mitotic response was increased around the amputation area but the regenerative blastema failed to form.ConclusionsWe demonstrate Akt signaling is essential for organismal physiology and in late stages of the Akt phenotype the reduction in neoblast numbers may impair regeneration in planarians. Functional disruption of Smed-Akt alters the balance between cell proliferation and cell death leading to systemic impairment of adult tissue renewal. Our results also reveal novel roles for Akt signaling during regeneration, specifically for the timely localization of cell death near the injury site. Thus, Akt signaling regulates neoblast biology and mediates in the distribution of injury-mediated cell death during tissue repair in planarians.Electronic supplementary materialThe online version of this article (doi:10.1186/s12861-016-0107-z) contains supplementary material, which is available to authorized users.
Highlights
Akt (PKB) is a serine threonine protein kinase downstream of the phosphoinositide 3-kinase (PI3K) pathway
Smed-Akt is widely expressed in neoblasts and differentiated cells and functional downregulation with RNAinterference [Smed-Akt(RNAi)] led to the reduction of neoblast numbers and loss of planarian locomotion [22]
To further characterize the effects of Akt downregulation on the cell cycle dynamics, we evaluated the incorporation of the bromodeoxyuridine analog (BrdU) every ten days for one month (Fig. 1d)
Summary
Akt (PKB) is a serine threonine protein kinase downstream of the phosphoinositide 3-kinase (PI3K) pathway. There is limited understanding of how Akt signaling controls the response of stem cells during cellular turnover and tissue injury in the complexity of the whole organism. This paucity is likely due to the ubiquitous nature of this signaling pathway and the difficulty of analyzing stem cells in their natural environment during physiological cell turnover and regeneration in conventional animal models [15,16,17]. We sought to investigate Akt function during cellular turnover and injury using the planarian flatworm Schmidtea mediterranea This organism is well known for its stem cell-based regenerative capability. This study defined the role of Smed-Akt in abnormal cell proliferation triggered by the abrogation of the phosphatase PTEN, an upstream component of the Akt signaling pathway, which is highly mutated in human cancers
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
