MROH2B (maestro heat-like repeat family member 2B ) is part of a novel complex that undergoes conformational and phosphorylation changes upon capacitation. — ASN Events

MROH2B (maestro heat-like repeat family member 2B ) is part of a novel complex that undergoes conformational and phosphorylation changes upon capacitation. (#227)

Simone J Stanger 1 2 3 , Duangporn Jamsai 4 , Moira K O'Bryan 4 , Brett Nixon 1 2 3 , Eileen A McLaughlin 1 2 3 , John Aitken 1 3 , Shaun D Roman 1 2 3
  1. School of Environmental & Life Sciences, The University of Newcastle, Callaghan, NSW, Australia
  2. The Priority Research Centre for Chemical Biology, The University of Newcastle,, Callaghan, NSW, Australia
  3. The Priority Research Centre for Reproductive Science, The University of Newcastle, Callaghan, NSW, Australia
  4. The Department of Anatomy and Developmental Biology, Monash University, Melbourne, Vic, Australia

Spermatozoa require the process of capacitation to enable them to fertilise an egg. Protein Kinase A (PKA) is crucial to capacitation and the development of hyperactivated motility and is an attractive target for the molecular characterisation of intracellular germ cell signalling. Sperm PKA is activated by cyclic adenosine monophosphate (cAMP) generated by the germ cell-specific soluble adenyl cyclase (sAC) encoded by Adcy10.  Mice lacking Adcy10 are sterile as their spermatozoa are immotile. Using the sperm specific (Ca2) catalytic subunit of PKA by using it as the ‘bait’ in a yeast-two hybrid system ach a novel germ cell enriched protein was identified and its sequence aligned to maestro heat-like repeat family member 2B (MROH2B). Homozygous Mroh2b null mice were embryonic lethal. Heterozygous deletion led to non-Mendelian inheritance in favour of mutant allele carrying offspring. The distorted inheritance was similar to transmission ratio distortion, a phenomenon found for other genes important for sperm function. MROH2B was co-expressed and co-regulated with PKA C and with TCP11, a gene known to modify transmission ratio distortion. We established that these three proteins form part of a novel complex in mouse spermatozoa. Upon capacitation the MROH2B protein was tyrosine phosphorylated and the complex undergoes a molecular rearrangement bringing PKA C and TCP11 into close proximity. These results suggest a role for a complex of MROH2B, PKA C and TCP11 during capacitation, fertilisation and embryogenesis.