Sperm’s sensitive steering machinery

Pichlo et al. describe how sea urchin sperm respond to tiny amounts of chemoattractant.

Sea urchin sperm are incredibly sensitive, being able to detect and respond to single molecules of chemoattractant as they navigate toward the egg. The guanylyl cyclase (GC) chemoreceptor localizes to the sperm flagellum where, upon binding to chemoattractant, the GC synthesizes the second messenger cGMP; in turn, the rise of cGMP activates ion channels in the flagellar membrane. Ca²⁺ ions flow into the flagellum, which alters the sperm’s swimming path. But how the chemoreceptor manages to respond to picomolar chemoattractant concentrations is unknown.

Pichlo et al. estimated that each sperm flagellum contains ∼300,000 GC chemoreceptors, enough to cover about 15% of the flagellum surface. Bacteria, in contrast, have a much lower density of chemoreceptors on their cell membrane and can only respond to micromolar concentrations of chemoattractant.

Not surprisingly, the GC chemoreceptor binds to its ligand with extremely high affinity. But Pichlo et al. found that this affinity decreases as more receptors become occupied. This allows sperm to dial down their sensitivity as they near the egg, preventing the chemoreceptors from becoming saturated so that they can continue to operate in the presence of higher chemoattractant concentrations.

The receptor’s high ligand-binding affinity might cause the chemoattractant to activate the receptor for extended periods, disrupting the sperm’s ability to navigate up the chemotactic gradient. Pichlo et al. found that each chemoreceptor is deactivated by dephosphorylation within 150 milliseconds of binding to its ligand. This deactivation may be permanent, but ample chemoreceptors remain to guide the sperm further along its path. Senior author Benjamin Kaupp now wants to investigate how the ∼300,000 chemoreceptors are organized within the sperm flagellum.