Calaxin drives sperm chemotaxis by Ca²⁺-mediated direct modulation of a dynein motor

Abstract

Sperm chemotaxis occurs widely in animals and plants and plays an important role in the success of fertilization. Several studies have recently demonstrated that Ca²⁺ influx through specific Ca²⁺ channels is a prerequisite for sperm chemotactic movement. However, the regulator that modulates flagellar movement in response to Ca²⁺ is unknown. Here we show that a neuronal calcium sensor, calaxin, directly acts on outer-arm dynein and regulates specific flagellar movement during sperm chemotaxis. Calaxin inhibition resulted in significant loss of sperm chemotactic movement, despite normal increases in intracellular calcium concentration. Using a demembranated sperm model, we demonstrate that calaxin is essential for generation and propagation of Ca²⁺-induced asymmetric flagellar bending. An in vitro motility assay revealed that calaxin directly suppressed the velocity of microtubule sliding by outer-arm dynein at high Ca²⁺ concentrations. This study describes the missing link between chemoattractant-mediated Ca²⁺ signaling and motor-driven microtubule sliding during sperm chemotaxis.