A novel neuronal calcium sensor family protein, calaxin, is a potential Ca²⁺‐dependent regulator for the outer arm dynein of metazoan cilia and flagella

Abstract

Background information. Spermatozoa show several changes in flagellar waveform, such as upon fertilization. Ca 2+ has been shown to play critical roles in modulating the waveforms of sperm flagella. However, a Ca 2+ -binding protein in sperm flagella that regulates axonemal dyneins has not been fully characterized.Results. We identified a novel neuronal calcium sensor family protein, named calaxin (Ca 2+ -binding axonemal protein), in sperm flagella of the ascidian Ciona intestinalis. Calaxin has three EF-hand Ca 2+ -binding motifs, and its orthologues are present in metazoan species, but not in yeast, green algae or plant. Immunolocalization revealed that calaxin is localized near the outer arm of the sperm flagellar axonemes. Moreover, it is distributed in adult tissues bearing epithelial cilia. An in vitro binding experiment indicated that calaxin binds to outer arm dynein. A cross-linking experiment showed that calaxin binds to β-tubulin in situ. Overlay experiments further indicated that calaxin binds the β-dynein heavy chain of outer arm dynein in the presence of Ca 2+ .Conclusions. These results suggest that calaxin is a potential Ca 2+ -dependent modulator of outer arm dynein in metazoan cilia and flagella.

Roles of extracellular ions and pH in 5-HT-induced sperm motility in marine bivalve

“…[Ca 2C ] i plays key role in the regulation of flagellar beating (Darszon et al 2011). Ca 2C -dependent or CaM protein phosphatase(s) are found in flagella of sea urchin, ascidian, fish, and mammals including human sperm (Nomura et al 2004, Marín-Briggiler et al 2005, Mizuno et al 2009. Similarly, sperm motility in marine bivalve mollusks was suppressed in the presence of CaM protein phosphodiesterase antagonist.…”

Flagellar ion channels of sperm: similarities and differences between species

“…The maintenance and regulation of intracellular calcium concentration ([Ca 2+ ] i ), is therefore, of great importance and is carried out by proteins and co-factors that import, export and/or sequester calcium ions [50]. In spermatozoa, swimming behavior is controlled by rises in [Ca 2+ ] i that changes flagellar beat pattern through Ca 2+ sensing proteins calaxins [51,52]. Calciumbound calaxins inhibit the activity of dynein motors within the Murine potassium channel KSper comprised of the Slo3 channel and associated gamma subunit LRRC52, as well as possible beta subunits.…”

Calcium Channels in the Development, Maturation, and Function of Spermatozoa

“…Pharmacological evidence indicates that CaMKII and/or CaMKIV is involved in this process in mammalian sperm (269,344). Recently, a novel Ca 2ϩ -binding protein, named calaxin, was identified as an axoneme component in sea squirt sperm (365). Bioinformatics revealed that calaxin belongs to the neuronal calcium sensor protein family.…”