RRC ID 56176
Author Kadekar P, Chaouni R, Clark E, Kazanets A, Roy R.
Title Genome-wide surveys reveal polarity and cytoskeletal regulators mediate LKB1-associated germline stem cell quiescence.
Journal BMC Genomics
Abstract BACKGROUND:Caenorhabditis elegans can endure long periods of environmental stress by altering their development to execute a quiescent state called "dauer". Previous work has implicated LKB1 - the causative gene in the autosomal dominant, cancer pre-disposing disease called Peutz-Jeghers Syndrome (PJS), and its downstream target AMPK, in the establishment of germline stem cell (GSC) quiescence during the dauer stage. Loss of function mutations in both LKB1/par-4 and AMPK/aak(0) result in untimely GSC proliferation during the onset of the dauer stage, although the molecular mechanism through which these factors regulate quiescence remains unclear. Curiously, the hyperplasia observed in par-4 mutants is more severe than AMPK-compromised dauer larvae, suggesting that par-4 has alternative downstream targets in addition to AMPK to regulate germline quiescence.
RESULTS:We conducted three genome-wide RNAi screens to identify potential downstream targets of the protein kinases PAR-4 and AMPK that mediate dauer-dependent GSC quiescence. First, we screened to identify genes that phenocopy the par-4-dependent hyperplasia when compromised by RNAi. Two additional RNAi screens were performed to identify genes that suppressed the germline hyperplasia in par-4 and aak(0) dauer larvae, respectively. Interestingly, a subset of the candidates we identified are involved in the regulation of cell polarity and cytoskeletal function downstream of par-4, in an AMPK-independent manner. Moreover, we show that par-4 temporally regulates actin cytoskeletal organization within the dauer germ line at the rachis-adjacent membrane, in an AMPK-independent manner.
CONCLUSION:Our data suggest that the regulation of the cytoskeleton and cell polarity may contribute significantly to the tumour suppressor function of LKB1/par-4.
Volume 19(1)
Pages 462
Published 2018-6-15
DOI 10.1186/s12864-018-4847-y
PII 10.1186/s12864-018-4847-y
PMID 29907081
PMC PMC6003023
MeSH AMP-Activated Protein Kinase Kinases Actin Cytoskeleton / ultrastructure* Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans / ultrastructure Caenorhabditis elegans Proteins / genetics* Cell Polarity / genetics Cytoskeleton Genome Germ Cells / cytology* Germ Cells / ultrastructure Hyperplasia Larva / cytology Larva / genetics Larva / ultrastructure Mutation Protein Kinases / genetics Protein Serine-Threonine Kinases / genetics* RNA Interference Stem Cells / cytology*
IF 3.501
Times Cited 3
C.elegans tm1944