title: Lipocalin 2 binds to membrane phosphatidylethanolamine to induce lipid raft movement in a PKA-dependent manner and modulates sperm maturation.
abstract: Mammalian sperm undergo multiple maturation steps after leaving the testis in order to become competent for fertilization, but the molecular mechanisms underlying this process remain unclear. In terms of identifying factors crucial for these processes in vivo, we found that lipocalin 2 (Lcn2), which is known as an innate immune factor inhibiting bacterial and malarial growth, can modulate sperm maturation. Most sperm that migrated to the oviduct of wild-type females underwent lipid raft reorganization and glycosylphosphatidylinositol-anchored protein shedding, which are signatures of sperm maturation, but few did so in Lcn2 null mice. Furthermore, we found that LCN2 binds to membrane phosphatidylethanolamine to reinforce lipid raft reorganization via a PKA-dependent mechanism and promotes sperm to acquire fertility by facilitating cholesterol efflux. These observations imply that mammals possess a mode for sperm maturation in addition to the albumin-mediated pathway.
authors.affiliation: Laboratory of Animal Experiments for Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Hitomi
authors.initials: H
authors.lastname: Watanabe
authors.forename: Toru
authors.initials: T
authors.lastname: Takeo
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Tojo
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Sakoh
authors.forename: Thorsten
authors.initials: T
authors.lastname: Berger
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.forename: Tak W
authors.initials: TW
authors.lastname: Mak
authors.forename: Gen
authors.initials: G
authors.lastname: Kondoh
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016466:CHO Cells; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D005260:Female; D005298:Fertility / Q000235:genetics; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008560:Membrane Fluidity / Q000235:genetics; D021962:Membrane Microdomains / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009068:Movement; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010714:Phosphatidylethanolamines / Q000378:metabolism*; D011247:Pregnancy; D011485:Protein Binding / Q000502:physiology; D013079:Sperm Maturation / Q000235:genetics*
chemical_list: D000209:Acute-Phase Proteins; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D010714:Phosphatidylethanolamines; C071332:Lcn2 protein, mouse; C483858:phosphatidylethanolamine; D002784:Cholesterol; D017868:Cyclic AMP-Dependent Protein Kinases
keywords: LCN2; Lipid raft; Mouse; Oviduct; PKA; Phosphatidylethanolamine; Sperm