Mating behavior, male sensory cilia, and polycystins in Caenorhabditis elegans

Abstract

The investigation of Caenorhabditis elegans males and the male-specific sensory neurons required for mating behaviors has provided insight into the molecular function of polycystins and mechanisms that are needed for polycystin ciliary localization. In humans, polycystin 1 and polycystin 2 are needed for kidney function; loss of polycystin function leads to autosomal dominant polycystic kidney disease (ADPKD). Polycystins localize to cilia in C. elegans and mammals, a finding that has guided research into ADPKD. The discovery that the polycystins form ciliary receptors in male-specific neurons needed for mating behaviors has also helped to unlock insights into two additional exciting new areas: the secretion of extracellular vesicles; and mechanisms of ciliary specialization. First, we will summarize the studies done in C. elegans regarding the expression, localization, and function of the polycystin 1 and 2 homologs, LOV-1 and PKD-2, and discuss insights gained from this basic research. Molecules that are co-expressed with the polycystins in the male-specific neurons may identify evolutionarily conserved molecular mechanisms for polycystin function and localization. We will discuss the finding that polycystins are secreted in extracellular vesicles that evoke behavioral change in males, suggesting that such vesicles provide a novel form of communication to conspecifics in the environment. In humans, polycystin-containing extracellular vesicles are secreted in urine and can be taken up by cilia, and quickly internalized. Therefore, communication by polycystin-containing extracellular vesicles may also use mechanisms that are evolutionarily conserved from nematode to human. Lastly, different cilia display structural and functional differences that specialize them for particular tasks, despite the fact that virtually all cilia are built by a conserved intraflagellar transport (IFT) mechanism and share some basic structural features. Comparative analysis of the male-specific cilia with the well-studied cilia of the amphid and phasmid neurons has allowed identification of molecules that specialize the male cilia. We will discuss the molecules that shape the male-specific cilia. The cell biology of cilia in male-specific neurons demonstrates that C. elegans can provide an excellent model of ciliary specialization.

Keywords: Cilia; Ciliopathies; Mating behavior; Polycystins; Sensory biology; TRP channel.

Fig. 1. A Diagram Of The Polycystin-Expressing Male-Specific Neurons In C. elegans

(Top panel) Bilateral pairs of dorsal and ventral CEM neurons have cell bodies anterior to the terminal bulb of the pharynx, and extend dendrites to the tip of the nose. The approximate locations of the HOB neuron and the 16 polycystin expressing RnB neurons of the tail are shown. The HOB extends a dendrite to a hook structure anterior to the tail fan. The RnB neurons extend dendrites into the rays of the tail fan. (Bottom Panels) Expression of LOV-1::GFP under the endogenous promoter illuminates the cell bodies of CEM in the head (left), and the HOB and RnB neurons in the tail (right). LOV-1::GFP fluorescence is faintly visible in the sensory cilia.

Fig. 2. The functional Domains Of Human And C. elegans Polycystins

Human polycystin 1 (PC1) and polycystin 2 (PC2) are shown on top. Domains of C. elegans polycystin 1 homolog LOV-1 and polycystin 2 homolog PKD-2 are shown on bottom. All diagrams are of equal scale, shown bottom right. Boxed areas indicate regions homologous to TRPP ion channel proteins. Note that all four contain homology to TRP ion channels, but only polycystin 2 and PKD-2 possess a voltage sensitive 4^th TM domain. (Abbreviations: LRR: Leucine-Rich Repeat; WSC: cell wall integrity and stress response component; PKD: polycystic kidney disease domain; GPS: GPCR proteolytic site; TM: transmembrane; PLAT: polycystin/lipoxygenase/α-toxin; ST rich: serine-threonine rich.)

Fig. 3. Polycystin-Containing ECVs Are Secreted By Ciliated Neurons Into The Environment

Top Panel shows a diagram of CEM neurons in the head secreting tiny vesicles out of the ciliary pore. Bottom Panel is a diagram of the structure of CEM cilia, surrounded by glial sheath and socket cells. ECVs are visible in the space between the CEM ciliary base and the sheath cell. ECVs are thought to travel along the cilium to be released into the environment through the ciliary pore. Modified from Wang et al. 2014.