Demonstration of a Functional Kisspeptin/Kisspeptin Receptor System in Amphioxus With Implications for Origin of Neuroendocrine Regulation

Abstract

Amphioxus belongs to the Cephalochordata, which is the most basal subphylum of the chordates. Despite many studies on the endocrine system of amphioxus, key information about its regulation remains ambiguous. Here we clearly demonstrate the presence of a functional kisspeptin/kisspeptin receptor (Kiss-Kissr) system, which is involved in the regulation of reproduction in amphioxus. Evolutionary analyses revealed large expansion of Kiss and Kissr (gpr54) genes in amphioxus, and they might represent the ancestral type of the Kiss/gpr54 genes in chordates. Amphioxus Kiss was obviously expression at the cerebral vesicle and the Hatschek pit, whereas amphioxus gpr54 messenger RNA (mRNA) was abundantly present in nerve cord, ovary, and testes. Amphioxus GPR54-Like1 (GPR54L-1) was shown to be located on the cell membrane. The synthetic amphioxus Kiss-like (KissL) peptides were capable of activating the amphioxus GPR54L-1 with different potencies, hinting the interaction between Kiss and GPR54. Moreover, the expression of amphioxus gpr54 mRNA was significantly decreased during low or high temperature extremes. Importantly, the injection of amphioxus KissL could cause an elevation of zebrafish blood luteinizing hormone level and induce the expression of amphioxus gpb5, a gene encoding the ancestral type of vertebrate pituitary glycoprotein hormones. Also, the expression levels of BjkissL-2 or Bjgpr54L-1 were downregulated after spermiation or spawning. Collectively, the amphioxus Kiss-Kissr system has a correlation with the regulation of reproduction. Our studies provide insights into the functional roles and evolutionary history of the Kiss-Kissr system, as well as the origin of the vertebrate neuroendocrine axis for controlling reproduction.

Evolution of neuropeptide signalling systems

“…Furthermore, it was discovered recently that, as with vertebrate calcitonin receptor-like receptors (CLRs), functional expression of a B. floridae calcitonin-type receptor requires coexpression of receptor activity-modifying proteins (RAMPs) ( Sekiguchi et al, 2016 ). Kisspeptin-type signalling pathways have also been characterised in B. floridae , providing evidence of an evolutionary ancient role for kisspeptins in regulation of reproductive activity ( Wang et al, 2017 ).…”

Eel Kisspeptins: Identification, Functional Activity, and Inhibition on both Pituitary LH and GnRH Receptor Expression

“…In the sea bass, Kp2(12), but not Kp1(15), can induce in vitro FSH release ( 73 ). Recently, it was reported that, in amphioxus ( Branchiostoma japonicum ), injection of amphioxus kisspeptin-like could upregulate the expression of gpb5 , a paralog of glycoprotein vertebrate-like β subunit ( 74 ). Our results on primary cultures of eel pituitary cells indicate that Kiss peptides may act directly at the pituitary cell levels in the eel.…”

Origin and Evolution of the Neuroendocrine Control of Reproduction in Vertebrates, With Special Focus on Genome and Gene Duplications

“…In B. floridae, one of the reported genes encodes three putative peptides, suggesting additional intragene duplication of peptidic sequences, while the other genes encode a single peptide (492). More recently, 27 putative KissR-like genes were identified in B. floridae (856). Further expression and functional studies were performed in the amphioxus B. japonicum on one kiss-like gene (BjkissL-2) and one kissR-like gene (Bjgpr54L-1) (856).…”

“…More recently, 27 putative KissR-like genes were identified in B. floridae (856). Further expression and functional studies were performed in the amphioxus B. japonicum on one kiss-like gene (BjkissL-2) and one kissR-like gene (Bjgpr54L-1) (856). Using quantitative PCR and immunohistochemistry, the authors showed that BjkissL-2 mRNA and protein levels are higher in notochord/nerve cord, and especially in the anterior region of the nerve cord (cerebral vesicle) and Hatschek's pit (856).…”