PAN-1 is a novel nematode-specific leucine-rich (LRR) protein that exhibits complexity in both structure and function. The
pan-1 gene encodes three protein isoforms: a predicted type I transmembrane protein with extracellular LRRs and two cytoplasmic proteins, one with a smaller number of LRRs and one lacking LRRs. PAN-1 participates in multiple developmental processes. It associates with P-granules in the germline (Gao et al, 2012) and is also required for larval development. For the latter,
pan-1 is necessary for early larval development and the L4 to adult transition.
pan-1 promotes growth of the germline, somatic gonad, and vulva during later larval stages and is required for progression of the L4 to adult molting cycle. To better understand the function of PAN-1 during larval development we have initiated a series of studies to address the cellular activities of this protein. Expression of the transmembrane isoform of PAN-1 lacking a cytoplasmic domain is dominant-negative, indicating that PAN-1 may dimerize and transduce an intracellular signal. Using these dominant-negative effects as an assay, we are performing conditional expression of different cytoplasmic domain-deleted constructs to identify critical regions of the intracellular domain. We are also characterizing interactions between
pan-1 and other genes. We have found that
lin-29 loss of function suppresses the molting progression and vulva development phenotypes in
pan-1 RNAi animals. We are further characterizing this interaction to determine how
pan-1 intersects with
lin-29 in molting regulation. In addition, loss of function of
lron-12, which encodes a secreted LRR protein, enhances the
pan-1 RNAi phenotype.
lron-12 mutants exhibit a larval growth phenotype indicating that
pan-1 and
lron-12 function together to regulate larval development. We propose that PAN-1 participates in a novel nematode-specific signaling pathway regulating life cycle progression.