C. elegans PTEN and AMPK block neuroblast divisions by inhibiting a BMP-insulin-PP2A-MAPK pathway

Author:

Zheng Shanqing1,Qu Zhi1,Zanetti Michael1,Lam Brandon1,Chin-Sang Ian1ORCID

Affiliation:

1. Department of Biology, Queen's University, Kingston, ON, Canada K7L 3N6

Abstract

ABSTRACT Caenorhabditis elegans that hatch in the absence of food stop their postembryonic development in a process called L1 arrest. Intriguingly, we find that the postembryonic Q neuroblasts divide and migrate during L1 arrest in mutants that have lost the energy sensor AMP-activated protein kinase (AMPK) or the insulin/IGF-1 signaling (IIS) negative regulator DAF-18/PTEN. We report that DBL-1/BMP works upstream of IIS to promote agonistic insulin-like peptides during L1 arrest. However, the abnormal Q cell divisions that occur during L1 arrest use a novel branch of the IIS pathway that is independent of the terminal transcription factor DAF-16/FOXO. Using genetic epistasis and drug interactions we show that AMPK functions downstream of, or in parallel with DAF-18/PTEN and IIS to inhibit PP2A function. Further, we show that PP2A regulates the abnormal Q cell divisions by activating the MPK-1/ERK signaling pathway via LIN-45/RAF, independently of LET-60/RAS. PP2A acts as a tumor suppressor in many oncogenic signaling cascades. Our work demonstrates a new role for PP2A that is needed to induce neuroblast divisions during starvation and is regulated by both insulin and AMPK.

Funder

Natural Sciences and Engineering Research Council of Canada

Canadian Institutes of Health Research

Publisher

The Company of Biologists

Subject

Developmental Biology,Molecular Biology

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