Male infertility-linked point mutation reveals a vital binding role for the C2 domain of sperm PLCζ

Male infertility-linked point mutation disrupts the Ca2+ oscillation-inducing and PIP2 hydrolysis activity of sperm PLCζ

A male infertility-linked human PLCζ (phospholipase Cζ) mutation introduced into mouse PLCζ completely abolishes both in vitro PIP(2) (phosphatidylinositol 4,5-bisphosphate) hydrolysis activity and the ability to trigger in vivo Ca2+ oscillations in mouse eggs. Wild-type PLCζ initiated a normal pattern of Ca2+ oscillations in eggs in the presence of 10-fold higher mutant PLCζ, suggesting that i...

A maternally inherited autosomal point mutation in human phospholipase C zeta (PLCζ) leads to male infertility.

BACKGROUND Male factor and idiopathic infertility contribute significantly to global infertility, with abnormal testicular gene expression considered to be a major cause. Certain types of male infertility are caused by failure of the sperm to activate the oocyte, a process normally regulated by calcium oscillations, thought to be induced by a sperm-specific phospholipase C, PLCzeta (PLCζ). Prev...

The role of sperm DNA testing on male infertility

Surgical sperm retrieval for male infertility

The C2 Domain of PKCδ Is a Phosphotyrosine Binding Domain

In eukaryotic cells, the SH2 and PTB domains mediate protein-protein interactions by recognizing phosphotyrosine residues on target proteins. Here we make the unexpected finding that the C2 domain of PKC directly binds to phosphotyrosine peptides in a sequence-specific manner. We provide evidence that this domain mediates PKC interaction with a Src binding glycoprotein, CDCP1. The crystal struc...