title: Regulation of metamorphosis in ascidians involves NO/cGMP signaling and HSP90.
abstract: Treatment of larvae of the ascidians Boltenia villosa (Family: Pyuridae) and Cnemidocarpa finmarkiensis (Family: Styelidae) with drugs that inhibit the function of the molecular chaperone HSP90 increased the frequency of tail resorption, the primary morphogenetic event of metamorphosis. If treatment was initiated at hatching, metamorphic events subsequent to tail resorption failed to occur, indicating an ongoing role for HSP90 during morphogenesis. Removal of tails from heads of mature, but not newly hatched larvae, induced metamorphosis of the head. Decapitation experiments indicate that the capacity of tails to shorten in response to inhibition of HSP90 function requires communication with heads. To identify candidate proteins with which HSP90 may interact to regulate metamorphosis, we noted that in mammalian cells, nitric oxide synthase (NOS) interacts with HSP90 and its activity is sensitive to drugs that inhibit HSP90 function. In addition, nitric oxide (NO) signaling in the marine snail Ilyanassa obsoleta is an important regulator of metamorphosis. Inhibition of NOS activity in these ascidian larvae with L-NAME increased the frequency of metamorphosis, consistent with a putative interaction of NOS and HSP90. NOS is present in tail muscle cells, implicating them as targets for the drug treatments, consistent with the decapitation experiments. Inhibition of soluble guanylyl cyclase, the most common effector of NO signaling, also increased the frequency of metamorphosis. In contrast to treatment with anti-HSP90 drugs, metamorphosis induced with L-NAME or ODQ was complete. The results presented suggest that an HSP90-dependent, NO-based regulatory mechanism localized in tails represses ascidian metamorphosis. We discuss these results in relation to the induction of ascidian metamorphosis by several unrelated agents.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: C D
authors.initials: CD
authors.lastname: Bishop
authors.forename: W R
authors.initials: WR
authors.lastname: Bates
authors.forename: B P
authors.initials: BP
authors.lastname: Brandhorst
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000494:pharmacology*; D018841:HSP90 Heat-Shock Proteins / Q000494:pharmacology*; D007814:Larva / Q000254:growth & development; D008675:Metamorphosis, Biological; D009569:Nitric Oxide / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D015398:Signal Transduction; D013623:Tail / Q000254:growth & development; D014561:Urochordata / Q000254:growth & development* / Q000502:physiology
chemical_list: D018841:HSP90 Heat-Shock Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP