title: LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility.
abstract: Male infertility affects at least 5% of reproductive age males. The most common pathology is a complex presentation of decreased sperm output and abnormal sperm shape and motility referred to as oligoasthenoteratospermia (OAT). For the majority of OAT men a precise diagnosis cannot be provided. Here we demonstrate that leucine-rich repeats and guanylate kinase-domain containing isoform 1 (LRGUK-1) is required for multiple aspects of sperm assembly, including acrosome attachment, sperm head shaping and the initiation of the axoneme growth to form the core of the sperm tail. Specifically, LRGUK-1 is required for basal body attachment to the plasma membrane, the appropriate formation of the sub-distal appendages, the extension of axoneme microtubules and for microtubule movement and organisation within the manchette. Manchette dysfunction leads to abnormal sperm head shaping. Several of these functions may be achieved in association with the LRGUK-1 binding partner HOOK2. Collectively, these data establish LRGUK-1 as a major determinant of microtubule structure within the male germ line.
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.
authors.forename: Kathleen
authors.initials: K
authors.lastname: DeBoer
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: de Kretser
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia; MIMR-PHI Institute of Medical Research, Monash Medical Centre, Clayton, Australia.
authors.forename: Liza
authors.initials: L
authors.lastname: O'Donnell
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.
authors.forename: Anne E
authors.initials: AE
authors.lastname: O'Connor
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.
authors.forename: D Jo
authors.initials: DJ
authors.lastname: Merriner
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia; Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Hidenobu
authors.initials: H
authors.lastname: Okuda
authors.affiliation: Australian Phenomics Facility, The Australian National University, Canberra, Australia.
authors.forename: Belinda
authors.initials: B
authors.lastname: Whittle
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Jans
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
authors.forename: Athina
authors.initials: A
authors.lastname: Efthymiadis
authors.affiliation: MIMR-PHI Institute of Medical Research, Monash Medical Centre, Clayton, Australia.
authors.forename: Robert I
authors.initials: RI
authors.lastname: McLachlan
authors.affiliation: The Garvan Institute of Medical Research and St. Vincent's Hospital Clinical School, UNSW Australia, Sydney, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ormandy
authors.affiliation: Australian Phenomics Facility, The Australian National University, Canberra, Australia.
authors.forename: Chris C
authors.initials: CC
authors.lastname: Goodnow
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.
authors.forename: Duangporn
authors.initials: D
authors.lastname: Jamsai
authors.affiliation: Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.
authors.forename: Moira K
authors.initials: MK
authors.lastname: O'Bryan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D064652:Basal Bodies / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D051528:Guanylate Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007248:Infertility, Male / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D013091:Spermatogenesis; D013094:Spermatozoa / Q000166:cytology / Q000378:metabolism*; D013737:Testis / Q000166:cytology / Q000378:metabolism
chemical_list: C521349:Hook2 protein, human; D008869:Microtubule-Associated Proteins; D020033:Protein Isoforms; D051528:Guanylate Kinases; C000603419:LRGUK protein, human