Kisspeptin-10

Guo C, Wu G, Liu T

Journal of biochemical and molecular toxicology

In a cultured human esophageal-carcinoma cell line (KYSE150), lentiviral overexpression of kisspeptin-10 reduced cell proliferation and migration, promoted apoptosis, decreased cancer-stem-cell marker expression, and suppressed epithelial-to-mesenchymal transition; the effect was linked to inhibition of the SIX1/Wnt/beta-catenin signaling pathway and was reversed by SIX1 overexpression, indicating GPR54-linked kisspeptin-10 signaling modulates this proliferative/migratory pathway in vitro.

Shen S, Wang D, Liu H, He X, Cao Y, Chen J, et al.

Cell reports

Cryo-electron microscopy of the KISS1R receptor bound to its endogenous ligand kisspeptin-10 (compared with a synthetic analog) mapped the peptide-receptor binding interface at the receptor's extracellular loops and identified a distinctive intracellular transmembrane-6 conformation underlying Gq-protein coupling, defining the structural basis of KISS1R activation at a molecular mechanistic level.

Torres E, Pellegrino G, Granados-Rodríguez M, Fuentes-Fayos AC, Velasco I, Coutteau-Robles A, et al.

The Journal of clinical investigation

Using astrocyte cultures from mouse, rat, and human tissue plus a conditional Kiss1r-knockout mouse line, this study found kisspeptin activates canonical intracellular signaling in kisspeptin-receptor-expressing astrocytes, and that receptor deletion in astrocytes altered astrocyte-GnRH neuron contacts, luteinizing-hormone pulsatility, and reproductive-axis responses to metabolic stress in the mouse model, identifying a non-neuronal glial signaling pathway contributing to hypothalamic-pituitary-gonadal axis regulation.

Simon C, Soga T, Parhar I

International journal of molecular sciences

In SH-SY5Y-derived cholinergic-like neurons engineered to overexpress wild-type or E46K-mutant alpha-synuclein, exogenous kisspeptin-10 exposure reduced alpha-synuclein-associated apoptosis and mitochondrial depolarization even when the GPR54 receptor was pharmacologically blocked, suggesting a receptor-independent binding interaction between kisspeptin-10 and alpha-synuclein in this cell-culture model of synucleinopathy.

Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, et al.

The Journal of biological chemistry

The original ligand-isolation study identified kisspeptins -- 54-, 14-, and 13-amino-acid RF-amide peptides derived from the KiSS-1 gene product and sharing the C-terminal decapeptide core common to kisspeptin-10 -- as natural agonists of the then-orphan G-protein-coupled receptor GPR54, purified from human placental tissue. In GPR54-expressing Chinese hamster ovary cell models, kisspeptins bound the receptor with low-nanomolar affinity and activated downstream signaling (PIP2 hydrolysis, calcium mobilization, ERK1/2 and p38 MAP-kinase phosphorylation), establishing the kisspeptin/GPR54 (KISS1R) ligand-receptor pair as a foundational discovery in this signaling pathway.