Rutgers professor sheds light on the role of microtubules based transport in mating behavior in C. elegans and its implication in humans

Maureen Barr, associate professor of genetics at Rutgers University, presented new developments in mating genetics in a seminar on Friday that described the role of microtubules and motors in the mating behavior of Caenorhabditis elegans. The mating behavior in C. elegans, a model organism, has been studied extensively, and while the genetic components that govern mating behavior remain elusive, recent discoveries have shed light on the problem of mating genetics, which may have implications in humans.

In male C. elegans, mating consists of an elaborate dance that includes detection of pheromones, wrapping around the partner, and location of the vulva. This process is achieved by four sensory neurons in the head, called the CEM (CEphalic neurons in Males) neurons, and four neurons in the tail of the male worm. The CEM neurons receive stimuli through cilia that protrude from the nose of the animal.

Barr investigated the mechanism of action of these CEM cilia through a genetic screen. She isolated male mutants that exhibited defective sexual behavior (i.e. could not sense a mate) but were normal in all other respects. She determined that these mutants showed abnormal activities in the proteins LOV-1 (LOcation of Vulva defective) and PKD-2 (Polycystic Kidney Disease), which are vital in characterizing male mating behavior.

Observation using GFP (Green Fluorescent Protein) revealed that these proteins were being transported by kinesin motors at an abnormally fast rate. Barr performed another genetic screen to look for aberrant ciliary localization activities and isolated a mutant that showed pooling of the two proteins in the head region of the worm. She determined that the mutation was located on the gene cil-6 (CIliary Localization). This gene codes for a metallocarboxypeptidase that detyrosinates alpha tubulin.

With these data, Barr hypothesized that CIL-6 must perform posttranslational modifications that affect the stability of the CEM microtubule tracks and therefore, affect the affinity of the kinesin motors to the tracks and their ability to transport LOV-1 and PKD-2 to their destinations.

Barr’s work extends beyond the realm of nematodes; the human counterpart to LOV-1 is PKD1, which encodes the protein polycystin-1. This protein is important in kidney function, where it localizes to the cilia in the apical regions of renal epithelial cells. Defects in polycystin protein may lead to polycystic kidney disease (PKD), which is characterized by the growth of numerous cysts in the kidneys.

In general, genetic defects in cilia are the basis of numerous developmental and physiological problems including obesity, male infertility, situs inversus, and polydactyly. Barr’s research highlights yet another important link between animal phenotypes and the intracellular transport system consisting of microtubules and motor proteins.