Reference - Detail
RRC ID | 46310 |
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Author | Nilsson L, Jonsson E, Tuck S. |
Title | Caenorhabditis elegans numb inhibits endocytic recycling by binding TAT-1 aminophospholipid translocase. |
Journal | Traffic |
Abstract |
Numb regulates endocytosis in many metazoans, but the mechanism by which it functions is not completely understood. Here we report that the Caenorhabditis elegans Numb ortholog, NUM-1A, a regulator of endocytic recycling, binds the C isoform of transbilayer amphipath transporter-1 (TAT-1), a P4 family adenosine triphosphatase and putative aminophospholipid translocase that is required for proper endocytic trafficking. We demonstrate that TAT-1 is differentially spliced during development and that TAT-1C-specific splicing occurs in the intestine where NUM-1A is known to function. NUM-1A and TAT-1C colocalize in vivo. We have mapped the binding site to an NXXF motif in TAT-1C. This motif is not required for TAT-1C function but is required for NUM-1A's ability to inhibit recycling. We demonstrate that num-1A and tat-1 defects are both suppressed by the loss of the activity of PSSY-1, a phosphatidylserine (PS) synthase. PS is mislocalized in intestinal cells with defects in tat-1 or num-1A function. We propose that NUM-1A inhibits recycling by inhibiting TAT-1C's ability to translocate PS across the membranes of recycling endosomes. |
Volume | 12(12) |
Pages | 1839-49 |
Published | 2011-12-1 |
DOI | 10.1111/j.1600-0854.2011.01271.x |
PMID | 21917090 |
MeSH | Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Adenosine Triphosphatases / metabolism Animals Binding Sites CDPdiacylglycerol-Serine O-Phosphatidyltransferase / metabolism Caenorhabditis elegans Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Endocytosis / genetics Endocytosis / physiology Endosomes / genetics Endosomes / metabolism Intestinal Mucosa / metabolism Membrane Transport Proteins / genetics Membrane Transport Proteins / metabolism Phospholipid Transfer Proteins / genetics Phospholipid Transfer Proteins / metabolism* Protein Binding Protein Interaction Domains and Motifs Protein Isoforms Protein Transport |
IF | 4.045 |
Times Cited | 16 |
WOS Category | CELL BIOLOGY |
Resource | |
C.elegans | tm1801 tm1275 tm1773 |