Adenosine Triggers Larval Settlement and Metamorphosis in the Mussel Mytilopsis sallei through the ADK-AMPK-FoxO Pathway

Abstract

Settlement and metamorphosis of planktonic larvae into benthic adults are critical components of a diverse range of marine invertebrate-mediated processes such as the formation of mussel beds and coral reefs, the recruitment of marine shellfisheries, and the initiation of macrobiofouling. Although larval settlement and metamorphosis induced by natural chemical cues is widespread among marine invertebrates, the mechanisms of action remain poorly understood. Here, we identified that the molecular target of adenosine (an inducer of larval settlement and metamorphosis from conspecific adults in the invasive biofouling mussel Mytilopsis sallei) is adenosine kinase (ADK). The results of transcriptomic analyses, pharmacological assays, temporal and spatial gene expression analyses, and siRNA interference, suggest that ATP-dependent phosphorylation of adenosine catalyzed by ADK activates the downstream AMPK-FoxO signaling pathway, inducing larval settlement and metamorphosis in M. sallei. This study not only reveals the role of the ADK-AMPK-FoxO pathway in larval settlement and metamorphosis of marine invertebrates but it also deepens our understanding of the functions and evolution of adenosine signaling, a process that is widespread in biology and important in medicine.

Signalling molecules inducing metamorphosis in marine organisms

“…Subsequent transcriptomic analyses together with temporal and spatial gene expression analyses and siRNA interference suggested that ATP-dependent phosphorylation of adenosine catalysed by ADK activates the downstream AMPK-FoxO signalling pathway. 137 Larvae of the scallop Pecten Natural Product Reports Review maximus were reported to respond to small molecules from red algae by settling on a free-standing water-covered surface. Active molecules were identied as catabolic derivatives of tyrosine (p-OH phenylacetic acid methyl ester (76), p-OH benzaldehyde (77), p-OH benzyl alcohol (78), homogentisic acid (79), as well as catecholamines (L-DOPA (40), epinephrine ( 17))) with jacaranone (75) being the most active component (Fig.…”

Integrated mRNA and miRNA transcriptomic analysis reveals the response of Rapana venosa to the metamorphic inducer (juvenile oysters)

“…In addition, conspecific adults and food also stimulate metamorphosis in some species. Metamorphosis stimulated by conspecific adults also occurs in some fouling species, such as Mytilopsis sallei and Balanus amphitrite [3] , [4] . Food-stimulated metamorphosis has been observed in some gastropods, such as the herbivorous gastropods Haliotis rufescens and Crepidula fornicata , whose metamorphosis is stimulated by their food species Lithophyllum sp.…”

“…Transcriptomics has been widely applied to investigate the mechanism underlying metamorphosis in invertebrates, including the mussel M. sallei , cnidarian Nematostella vectensis , pearl oyster Pinctada fucata and abalone Haliotis diversicolor [3] , [22] , [23] , [24] , revealing the critical pathway and genes regulating metamorphosis and providing novel insights into the metamorphosis mechanism in marine invertebrates. MicroRNAs (miRNAs) participate in RNA silencing and posttranscriptional gene expression regulation in eukaryotes [25] , [26] , providing further concrete support for conclusions drawn from the transcriptome; however, few studies have been conducted to investigate metamorphosis in marine invertebrates.…”

AMPK Promotes Larval Metamorphosis of Mytilus coruscus

“…During the metamorphosis process, the larvae go through many drastic morphological changes; for some marine mussels, this includes the disappearance of the face plate, the shedding of the ciliary ring, the rapid growth of gill filaments, and the production of adult shells so as to develop to post-larvae and grow into adults, which need to consume a large amount of energy [ 9 ]. Some investigations have indicated that α2-adrenergic receptors [ 6 ], nitric oxide [ 10 ], adenosine kinase [ 11 ], and other signals can govern the metamorphosis process of marine mussel larvae; however, the mechanism of metamorphosis remains poorly understood.…”