Calcium sensors of ciliary outer arm dynein: functions and phylogenetic considerations for eukaryotic evolution

Abstract

The motility of eukaryotic cilia and flagella is modulated in response to several extracellular stimuli. Ca2+ is the most critical intracellular factor for these changes in motility, directly acting on the axonemes and altering flagellar asymmetry. Calaxin is an opisthokont-specific neuronal calcium sensor protein first described in the sperm of the ascidian Ciona intestinalis. It binds to a heavy chain of two-headed outer arm dynein in a Ca2+-dependent manner and regulates ‘asymmetric’ wave propagation at high concentrations of Ca2+. A Ca2+-binding subunit of outer arm dynein in Chlamydomonas reinhardtii, the light chain 4 (LC4), which is a Ca2+-sensor phylogenetically different from calaxin, shows Ca2+-dependent binding to a heavy chain of three-headed outer arm dynein. However, LC4 appears to participate in ‘symmetric’ wave propagation at high concentrations of Ca2+. LC4-type dynein light chain is present in bikonts, except for some subclasses of the Excavata. Thus, flagellar asymmetry-symmetry conversion in response to Ca2+ concentration represents a ‘mirror image’ relationship between Ciona and Chlamydomonas. Phylogenetic analyses indicate the duplication, divergence, and loss of heavy chain and Ca2+-sensors of outer arm dynein among excavate species. These features imply a divergence point with respect to Ca2+-dependent regulation of outer arm dynein in cilia and flagella during the evolution of eukaryotic supergroups.

Particle sorting by Paramecium cilia arrays

“…When a paramecium collides with a solid object, for example, its membrane depolarises which precipitates Ca 2+ influx, leading to spontaneous reversal of ciliary beat direction [22,23]. This is considered to result from interactions between Ca 2+ ions and calcium-binding proteins which influence axonemal microtubule actuation [24].…”

Sperm dysfunction and ciliopathy

“…However, difference in the usage of axonemal proteins has been observed between Chlamydomonas and animal sperm [28,37,151]. The composition of the ODA-DC is likely different between sperm and Chlamydomonas flagella [40].…”

“…Similarly, knowledge has been accumulating showing that some axonemal components are specific to metazoans and do not exist in Chlamydomonas. For example, a calcium sensor for the OAD, calaxin, is specific to metazoan species [35,37]. The calcium sensor for OAD in Chlamydomonas is dynein LC4, which is present in most bikont species [37].…”

“…Several studies indicate that animal and Chlamydomonas flagella contain two and three HCs, respectively, in the OAD [11,37]. From their molecular substructures, these are referred to as two-headed or three-headed dyneins.…”

“…The OAD from animal sperm has two HCs, two WD-repeat ICs, a unique IC with thioredoxin and nucleoside diphosphate kinase domains [30][31][32], and regulatory LCs such as Tctex-2 LC [33,34] and a Ca 2? -binding protein named calaxin [35][36][37] (Fig. 1d).…”