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

Abstract

The investigation of C. 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.

Model Organisms in G Protein–Coupled Receptor Research

“…In both C. elegans and mammals, the polycystins localize to cilia and ciliary extracellular vesicles, where they are thought to act in a signaling capacity (O'Hagan et al, 2014;Wood and Rosenbaum, 2015). In humans, abnormalities in polycystin trafficking or stability may underlie autosomal dominant polycystic kidney disease (Cai et al, 2014).…”

“…has been using C. elegans as a model for studying mechanisms regulating the localization and functions of the polycystins in cilia and extracellular vesicles (O'Hagan et al, 2014;Wang et al, 2014). PC1 proteins, like aGPCRs, contain a GPCR autoproteolysis-inducing domain, undergo autoproteolytic cleavage at a GPS into N-terminal and C-terminal regions, and can activate G protein second messengers, endowing them with GPCR-like properties (Delmas et al, 2004;Yu et al, 2007;Prömel et al, 2013).…”

“…PC1 proteins, like aGPCRs, contain a GPCR autoproteolysis-inducing domain, undergo autoproteolytic cleavage at a GPS into N-terminal and C-terminal regions, and can activate G protein second messengers, endowing them with GPCR-like properties (Delmas et al, 2004;Yu et al, 2007;Prömel et al, 2013). LOV-1 possesses a GPS, and an N-terminal region lacking TM domains remains associated with cilia and extracellular vesicles, suggesting that LOV-1 may be an atypical aGPCR (Barr and Sternberg, 1999;O'Hagan et al, 2014;Wang et al, 2014).…”

Ciliary Extracellular Vesicles: Txt Msg Organelles

“…The C. elegans male has 383 neurons, sharing 60 ciliated sensory neurons with the hermaphrodite and also possessing 48 male-specific ciliated sensory neurons devoted to sexual behaviors (O'Hagan et al, 2014; Sulston et al, 1980). C. elegans males shed and release EVs from 27 ciliated e xtracellular v esicle releasing n eurons (EVNs) including six shared IL2 neurons and 21 male-specific polycystin-expressing EVNs in the head (four CEM neurons) and tail (16 ray B-type RnB neurons and one hook B-type HOB neuron)(Figure 1A)(Wang et al, 2014).…”

Middle Age Has Its Advantages

“…elegans cilia have human counterparts that, when mutated, cause ciliopathies [6,8,9]. Unlike mice or humans, worms lacking cilia are viable and fertile under laboratory conditions but exhibit severe sensory defects.…”