Pa. Witt-enderby et al., Melatonin induction of filamentous structures in non-neuronal cells that is dependent on expression of the human mt1 melatonin receptor, CELL MOTIL, 46(1), 2000, pp. 28-42
Melatonin has gained recent popularity as a treatment for insomnia and othe
r sleep disorders; however, its cellular effects are unknown. We report the
effects of melatonin on the cellular morphology of Chinese hamster ovary (
CHO) cells transformed to express the human melatonin receptors, mt1 and MT
2. Our results show that melatonin exerts a strong influence on cellular sh
ape and cytoskeletal organization in a receptor-dependent and possibly subt
ype-selective manner. The cell shape change that we see after a 5-h treatme
nt of these non-neuronal cells with a pharmacological concentration of mela
tonin consists of the formation of long filamentous outgrowths that are rem
iniscent of the neurite processes produced by differentiating nerve cells.
This morphological change occurs exclusively in cells expressing the mt1 re
ceptor. We find that the microtubule and microfilament organization within
these outgrowths is similar to that of neurites. Microtubules are required
for the shape change to occur as Colcemid added in combination with melaton
in completely blocks outgrowth formation. We demonstrate that the number of
cells showing the altered cell shape is dependent on melatonin concentrati
on, constant exposure to melatonin and that outgrowth frequencies increase
when protein kinase A (PKA) is inhibited. Concomitant melatonin-dependent i
ncreases in MEK 1/2 and ERK 1/2 phosphorylation are noted in mt1-CHO cells
only. The production of filamentous outgrowths is dependent on the translat
ion of new protein but not the transcription of new mRNA. Outgrowth number
is not controlled by centrosomes but is instead controlled by the polymeriz
ation state of the actin cytoskeleton. The results of his work show that th
e organization of the cytoskeleton is affected by processes specifically me
diated or regulated by the mt1 receptor and may represent a novel alternati
ve mechanism For the stimulation of process formation. (C) 2000 Wiley-Liss,
Inc.