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PLoS Genet. 2015 Mar 17;11(3):e1005090. doi: 10.1371/journal.pgen.1005090. eCollection 2015 Mar.

LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility.

Author information

1
Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia.
2
Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia; MIMR-PHI Institute of Medical Research, Monash Medical Centre, Clayton, Australia.
3
Department of Anatomy and Developmental Biology, School of Biomedical Sciences, Monash University, Australia; Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
4
Australian Phenomics Facility, The Australian National University, Canberra, Australia.
5
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia.
6
MIMR-PHI Institute of Medical Research, Monash Medical Centre, Clayton, Australia.
7
The Garvan Institute of Medical Research and St. Vincent's Hospital Clinical School, UNSW Australia, Sydney, Australia.

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.

PMID:
25781171
PMCID:
PMC4363142
DOI:
10.1371/journal.pgen.1005090
[Indexed for MEDLINE]
Free PMC Article

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