title: Rabconnectin-3α is required for the morphological maturation of GnRH neurons and kisspeptin responsiveness.
abstract: A few hundred hypothalamic neurons form a complex network that controls reproduction in mammals by secreting gonadotropin-releasing hormone (GnRH). Timely postnatal changes in GnRH secretion are essential for pubertal onset. During the juvenile period, GnRH neurons undergo morphological remodeling, concomitantly achieving an increased responsiveness to kisspeptin, the main secretagogue of GnRH. However, the link between GnRH neuron activity and their morphology remains unknown. Here, we show that brain expression levels of Dmxl2, which encodes the vesicular protein rabconnectin-3α, determine the capacity of GnRH neurons to be activated by kisspeptin and estradiol. We also demonstrate that Dmxl2 expression levels control the pruning of GnRH dendrites, highlighting an unexpected role for a vesicular protein in the maturation of GnRH neuronal network. This effect is mediated by rabconnectin-3α in neurons or glial cells afferent to GnRH neurons. The widespread expression of Dmxl2 in several brain areas raises the intriguing hypothesis that rabconnectin-3α could be involved in the maturation of other neuronal populations.
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, U1141, Inserm, F- 75019, Paris, France.
authors.forename: Brooke K
authors.initials: BK
authors.lastname: Tata
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, U1141, Inserm, F- 75019, Paris, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Harbulot
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, U1141, Inserm, F- 75019, Paris, France.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Csaba
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, U1141, Inserm, F- 75019, Paris, France.|MRC Centre for Synaptic Plasticity; School of Physiology, Pharmacology, Neurosciences; University of Bristol, Bristol, UK.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Peineau
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, U1141, Inserm, F- 75019, Paris, France.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Jacquier
authors.affiliation: Univ Paris Diderot, Sorbonne Paris Cité, U1141, Inserm, F- 75019, Paris, France.|AP-HP, Laboratoire de Biochimie. Hôpital Robert Debré, Paris, F-75019, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: de Roux
mesh_terms: D000818:Animals; D003712:Dendrites / Q000378:metabolism; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D017353:Gene Deletion; D015870:Gene Expression; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D059648:Kisspeptins / Q000378:metabolism* / Q000494:pharmacology; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D012741:Sexual Maturation
chemical_list: C576980:DMXL2 protein, mouse; D059648:Kisspeptins; D009419:Nerve Tissue Proteins; D007987:Gonadotropin-Releasing Hormone; D004958:Estradiol; D007986:Luteinizing Hormone