Liprin α3, LAR and its ligands in mouse spermatozoa

Zona pellucida-based induction of acrosome reaction (AR) is a popular and well-accepted hypothesis. However, this hypothesis is being challenged in recent years and it has been proposed that the cumulus cells might be the site of AR. In our previous study, we reported the presence of a synaptic protein Liprin 3 on sperm acrosome, and proposed its role in AR. This study was designed to understand the role of Liprin 3 and its interacting proteins in regulation of AR. It is observed that the presence of anti-Liprin 3 antibody inhibits the process of AR. Colocalization experiments demonstrate the coexistence of leucocyte antigen related (LAR) protein, Rab-interacting molecule (RIM) and Liprin 3 on sperm acrosome thereby completing the identification of all the members of RIM/MUNC/Rab3A/liprin complex required for membrane fusion. This study demonstrates the effect of LAR ligands such as Syndecans, Nidogens and LAR wedge domain peptide on AR. We could see an increase in AR in presence of these ligands. On the basis of these data, we speculate that in presence of ligands or wedge peptide, LAR undergoes dimerization leading to inhibition of phosphatase activity and increase in AR. The presence of one of the ligands Syndecan-1 on cumulus cells led us to hypothesize that it is Syndecan which induces AR in vivo and thus another site of AR could lie in cumulus.