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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Basal Bodies / metabolism
  • Cell Membrane / metabolism
  • Guanylate Kinases / chemistry
  • Guanylate Kinases / genetics
  • Guanylate Kinases / metabolism*
  • Humans
  • Infertility, Male / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Data
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Sequence Alignment
  • Spermatogenesis*
  • Spermatozoa / cytology
  • Spermatozoa / metabolism*
  • Testis / cytology
  • Testis / metabolism

Substances

  • Hook2 protein, human
  • Microtubule-Associated Proteins
  • Protein Isoforms
  • Guanylate Kinases
  • LRGUK protein, human

Grant support

This work was supported by grants from the NHMRC to (MKO, RIM, DMdK and CJO), the Australian Research Council (MKO, and CJO), the New South Wales Cancer Council (CJO), Cancer Institute New South Wales (CJO), Banque Nationale de Paris-Paribas Australia and New Zealand (CJO), RT Hall Trust (CJO), and the National Breast Cancer Foundation (CJO.) MKO, DAJ, RIM, CJO and CCG are the recipients of NHMRC Fellowships The Australian Phenomics Network is funded by the Australian Government through National Collaborative Research Infrastructure Strategy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.