Adaptor protein (AP) complexes mediate the association of cargo proteins with clathrin-coated vesicles (CCVs) to facilitate membrane trafficking along the secretory and endocytic pathways. Mammals possess four AP complexes (AP-1, -2, -3, -4), whereas three AP complexes (AP-1, -2, -3) are found in Drosophila, C. elegans, and yeast. All AP complexes form similar heterotetramers consisting of two large subunits (g/b1, a/b2, d/b3, e/b4, respectively), which facilitate membrane association and clathrin binding, one medium subunit (
m1 ~
m4), which mediates cargo recognition, and one small subunit (
s1~
s4), which provides complex stability. While the AP-1 and AP-2 complexes have well characterized roles in secretion from the Golgi and endocytosis at the plasma membrane, respectively, the functions of AP-3, and AP-4 complexes are less well understood (1, 2). Previous genetic findings in Drosophila, mouse, human, and yeast demonstrate a role for AP-3 complexes in the trafficking of proteins from the Golgi directly to lysosomes and lysosome-related organelles (e.g., melanosomes and platelet dense granules). In humans, loss of AP-3 function results in Hermansky-Pudlak syndrome (HPS), with the clinical symptoms of hypopigmentation, prolonged bleeding, and pulmonary fibrosis due to defects in the maturation of melanosomes and platelet dense granules (3). In C. elegans, AP-3 function was shown to be essential for embryogenesis and larval development (4). In addition, defects in the formation of lysosome-related gut granules were reported in mutants for AP-3 complex genes (5). Although the AP-3 complex is clearly involved in trafficking to lysosomes and their related organelles, the precise trafficking steps conducted by AP-3 complex still remain uncertain. In this study, we examined the trafficking and subcellular localization of multiple fluorescently tagged cargo proteins and endosomal/lysosomal markers in both C. elegans epithelial cells and neurons. We show that in addition to regulating gut granule formation, AP-3 complex also regulates several key membrane trafficking steps within multiple cell types. References 1. Boehm, M et al., Mol Biol. Cell 12, 2907-2920 (2001). 2. Nakatsu, et al., Cell Structure and Function 28, 419-429 (2003) 3. Dell'Angelica, E. C. et al., Mol. Cell 3, 11-21 (1999). 4. Shim, J. et al., Mol. Cell 19(3), 452-457 (2005). 5. Hermann, G. J. et al., Mol. Biol. Cell 16, 3273-3288 (2005)..