Previously, in Caenorhabditis elegans a conserved TGF-beta signaling pathway has been characterized (Riddle, 1997, Thomas, 2001). This pathway is known to control dauer formation behavior, similar to the
daf-2 insulin like signaling pathway. The
daf-7 encodes a homolog of the GDF-8 and is expressed in the chemosensory neuron ASI, and the type I and type II TGF beta Ser/Thr receptor kinases are encoded by
daf-1 and
daf-4. The downstream Smad proteins are encoded by
daf-8, and
daf-14 genes that couple the TGF beta signals from DAF-1 and DAF-4 receptor kinases to regulate transcription of downstream genes. We have examined the role of various components of the TGF beta pathway in albumin endocytosis in the intestinal epithelial cells in post-emb ryonic development, and described that mutations in
daf-1 and
daf-4 inhibit albumin endocytosis in the intestinal cells. Genetic analysis reveals that mutations in
daf-3 null mutation completely suppress the endocytosis defective phenotype of
daf-1,
daf-4 ,
daf-7 and
daf-8 mutations, suggesting an independent endocytosis pathway exposed by mutations in
daf-3. The
daf-3 encoded protein is homologous to vertebrate DPC4, a cofactor of Smad1, Smad2, and Smad3. In contrast, downstream components of the TGF-beta signaling that affect body size, such as
sma-2,
sma-3, and
sma-6 apparently have no effect on albumin endocytosis in the intestine. We thank D. Riddle, G. Ruvkun, C. Savage, J. Thomas and T. Stiernagle, CGC for strains and L. Jacobson for making the original observation that mutants in
daf-4 are defective in albumin uptake.