Endocytic Sorting and Recycling Require Membrane Phosphatidylserine Asymmetry Maintained by TAT-1/CHAT-1

University of California San Diego, United States of America
PLoS Genetics (Impact Factor: 7.53). 12/2010; 6(12):e1001235. DOI: 10.1371/journal.pgen.1001235
Source: PubMed


Author Summary
The process by which cells take up nutrients and other large molecules from the extracellular environment is known as endocytosis. At the cell surface, external molecules become enclosed in membrane spheres called endosomes. Early endosomes serve as a sorting station, directing the contents (cargo molecules) to the correct compartment within the cell. This is thought to be achieved by the formation of membrane structures with distinct shape and function. For example, cargoes destined for recycling and degradation are processed through tubular membrane structures and big vesicular compartments, respectively. However, it is poorly understood how early endosome membranes are shaped into different structures. Here we show that two proteins, CHAT-1 and TAT-1, regulate membrane structure and are important for normal endocytic transport in the nematode worm C. elegans. TAT-1 and CHAT-1 are found in tubular membrane structures along the sorting and recycling pathway, where they enrich the outer membrane layer with a lipid called phosphatidylserine (PS) and probably change the membrane curvature. Loss of tat-1 and chat-1 function disrupts the asymmetric distribution of PS, abolishes tubular membrane structures, and abrogates endocytic sorting/recycling. Our data support a role of TAT-1/CHAT-1–regulated membrane PS asymmetry in promoting membrane tubulation for endocytic cargo sorting and recycling.

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    • "The Caenorhabditis elegans P4-ATPase transbilayer amphipath transporter 1 (TAT-1) is required for yolk uptake in oocytes and for an early step of fluid-phase endocytosis in the intestine [22, 74]. TAT-1 forms a complex with the Cdc50 family protein CHAT-1, and both proteins are important in maintaining normal endocytic sorting/recycling by promoting membrane tubulation of the early endosome [12]. Further, TAT-5 has been linked to the regulation of ectosome shedding [100]. "
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    • "In addition, the Caenorhabditis elegans Drs2 orthologue Tat-1 localizes to recycling endosomes and is required for its tubular morphology and protein trafficking through this organelle (Ruaud et al., 2009; Chen et al., 2010). Thus, PS translocation by P4-ATPases appears to be a highly conserved mechanism for inducing membrane deformation to support vesicular transport. "
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    • "Slc16a10 has been previously reported as undetectable in the adult brain (Kinne et al., 2011). The TAT1 protein (Slc16a10, MCT10) has also been proposed to be involved in endocytotic membrane sorting and recycling (Chen et al., 2010); its expression in developing choroid plexus may be relevant to the proposed protein transport mechanism across the choroid plexus epithelial cells (Liddelow et al., 2011, and see Saunders et al., 2012 for earlier references). The monocarboxylate transporters MCT1 (Slc16a1) and MCT2 (Slc16a7) have been studied in embryonic and postnatal rat brain (Baud et al., 2003). "
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