RT Journal Article
SR Electronic
T1 ERK pathway activation inhibits ciliogenesis and causes defects in motor behavior, ciliary gating, and cytoskeletal rearrangement
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.05.18.492507
DO 10.1101/2022.05.18.492507
A1 Larissa L Dougherty
A1 Soumita Dutta
A1 Prachee Avasthi
YR 2022
UL http://biorxiv.org/content/early/2022/05/18/2022.05.18.492507.abstract
AB Mitogen-activated protein kinase (MAPK) pathways are well known regulators of the cell cycle but they have also been found to control ciliary length in a wide variety of organisms and cell types from Caenorhabditis elegans neurons to mammalian photoreceptors through unknown mechanisms. ERK1/2 is a MAP kinase in human cells that is predominantly phosphorylated by MEK1/2 and dephosphorylated by the phosphatase DUSP6. We have found that the ERK1/2 activator/DUSP6 inhibitor, (E)-2-benzylidine-3-(cyclohexylamino)-2,3-dihydro-1H-inden-1-one (BCI), inhibits ciliary maintenance in Chlamydomonas and hTERT-RPE1 cells and assembly in Chlamydomonas. These effects involve inhibition of total protein synthesis, microtubule organization, membrane trafficking, and partial kinesin-2 motor dynamics. Our data provide evidence for various avenues for BCI-induced ciliary shortening and impaired ciliogenesis that gives mechanistic insight into how MAP kinases can regulate ciliary length.Competing Interest StatementPA is a paid consultant for Arcadia Science