The CIL-1 PI 5-phosphatase localizes TRP Polycystins to cilia and activates sperm in C. elegans.
BACKGROUND
C. elegans male sexual behaviors include chemotaxis and response to hermaphrodites, backing, turning, vulva location, spicule insertion, and sperm transfer, culminating in cross-fertilization of hermaphrodite oocytes with male sperm. The LOV-1 and PKD-2 transient receptor potential polycystin (TRPP) complex localizes to ciliated endings of C. elegans male-specific sensory neurons and mediates several aspects of male mating behavior. TRPP complex ciliary localization and sensory function are evolutionarily conserved. A genetic screen for C. elegans mutants with PKD-2 ciliary localization (Cil) defects led to the isolation of a mutation in the cil-1 gene.


RESULTS
Here, we report that a phosphoinositide (PI) 5-phosphatase, CIL-1, regulates TRPP complex ciliary receptor localization and sperm activation. cil-1 does not regulate the localization of other ciliary proteins, including intraflagellar transport (IFT) components, sensory receptors, or other TRP channels in different cell types. Rather, cil-1 specifically controls TRPP complex trafficking in male-specific sensory neurons and does so in a cell-autonomous fashion. In these cells, cil-1 is required for normal PI(3)P distribution, indicating that a balance between PI(3,5)P2 and PI(3)P is important for TRPP localization. cil-1 mutants are infertile because of sperm activation and motility defects. In sperm, the CIL-1 5-phosphatase and a wortmannin-sensitive PI 3-kinase act antagonistically to regulate the conversion of sessile spermatids into motile spermatozoa, implicating PI(3,4,5)P3 signaling in nematode sperm activation.


CONCLUSIONS
Our studies identify the CIL-1 5-phosphatase as a key regulator of PI metabolism in cell types that are important in several aspects of male reproductive biology.
Bae
Young-Kyung
YK
Department of Genetics, Rutgers University, the State University of New Jersey, Piscataway, NJ 08854, USA.
Kim
Eunsoo
E
L'hernault
Steven W
SW
Barr
Maureen M
MM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D016000:Cluster Analysis; D017931:DNA Primers / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D017422:Sequence Analysis, DNA; D012726:Sexual Behavior, Animal / Q000502:physiology*; D013094:Spermatozoa / Q000378:metabolism / Q000502:physiology*; D050396:TRPP Cation Channels / Q000378:metabolism*; D050051:Transient Receptor Potential Channels / Q000378:metabolism*; D000099182:Phosphoinositide 5-Phosphatases
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D010744:Phosphoric Monoester Hydrolases; D050396:TRPP Cation Channels; D050051:Transient Receptor Potential Channels; D000099182:Phosphoinositide 5-Phosphatases; C515011:LOV-1 protein, C elegans; C527777:PKD-2 protein, C elegans