RT Journal Article
SR Electronic
T1 The ERK activator, BCI, inhibits ciliogenesis and causes defects in motor behavior, ciliary gating, and cytoskeletal rearrangement
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202301899
DO 10.26508/lsa.202301899
VO 6
IS 6
A1 Larissa L Dougherty
A1 Soumita Dutta
A1 Prachee Avasthi
YR 2023
UL https://www.life-science-alliance.org/content/6/6/e202301899.abstract
AB 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-benzylidene-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 KAP-GFP 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.