In the C. elegans germ
line, Notch-type signaling regulates the switch from proliferation to meiosis. In adults, the somatic distal tip cell
(DTC) produces a DSL-type ligand, LAG-2, that activated the germline receptor,
GLP-1/Notch. In the absence of
GLP-1 signaling, germ cells exit mitosis, enter meiosis, and
differentiate.
ego-2(
om33) was recovered in a genetic screen for enhancers
of a weak
glp-1
mutation (Qiao et al., 1995,
Genetics 141:551-569). We cloned
ego-2 and determined the cDNA sequence. The predicted EGO-2 protein contains a
BRO1 domain, which is known to localize proteins to endosomes, and is related
to the Bro1p/Alix family of proteins that function in protein trafficking. The
ego-2(
om33) allele contains a single amino acid substitution at
a semi-conserved residue in the BRO1 domain. Phenotypic analyses suggest
ego-2 functions in both the soma and germ line.
ego-2(RNAi) causes slow growth and uncoordinated movement.
ego-2(
om33) and
ego-2(RNAi) enhance a weak
glp-1(lf)
in the embryo. In addition,
quantitative RT-PCR data indicate that
ego-2 mRNA is not germline-specific.
Impaired endocytosis in the signaling cell is known to
inhibit Notch-type signaling in various systems, including the C. elegans gonad (Tian et al., 2004, Development 131:5807-5815). We examined the ability of
ego-2(RNAi) to enhance
glp-1(ts) in a
rrf-1(0) background, where somatic RNAi is defective. Intriguingly,
glp-1(ts) was enhanced in these animals, but at a reduced level, suggesting that
EGO-2 function is important in both the DTC and germ line. Our working model is that EGO-2 may
have a protein trafficking/sorting function that promotes GLP-1 signaling
pathway activity in both the DTC and germ line. A second C. elegans BRO1 domain protein, ALX-1, interacts with LIN-12/Notch (Shaye &
Greenwald, 2005, Development 132:5081-5092).
alx-1(0) did
not enhance
glp-1(ts) in the germ
line, but did interact with
ego-2.
ego-2(
om33) mutants have a temperature-sensitive spermatogenesis
(Spe) defect, which is enhanced by
alx-1(0).
Therefore, the two genes may have partial functional redundancy. We hypothesize that the Spe defect may
arise from impaired trafficking of proteins required for the sperm-oocyte
interaction.