Sla1p recognizes the NPFXD endocytosis signal.

Cell surface receptors that are internalized generally interact with the endocytic machinery through adaptor proteins. On page 315, Howard et al. describe the first example of a protein involved in recognizing endocytic targeting signals in yeast. The work links together several earlier observations about yeast actin dynamics and endocytosis, and suggests that an analogous system may exist in mammalian cells.

The authors found that a sequence containing the amino acid motif NPFX(1,2)D, previously characterized as an endocytic targeting signal in yeast, is sufficient to direct the uptake of a truncated cell surface receptor. A two-hybrid screen for NPFX(1,2)D-binding proteins yielded Sla1p, which is known to interact with the endocytic machinery and regulate actin dynamics. Disrupting Sla1p expression inhibited NPFX(1,2)D-mediated endocytosis.

Combined with previous findings, the results imply that Sla1p is part of a complex that links cargo bearing the NPFX(1,2)D motif to the actin and clathrin-based endocytic machinery. By analogy, a similar complex in mammalian cells might provide a Sla1p-like adaptor function in endocytosis. Searches of the yeast genome database suggest that NPFX(1,2)D directs endocytosis of a subset of cell surface proteins, and may also mediate other types of protein sorting. ▪