Caenorhabditis elegans Numb Inhibits Endocytic Recycling by Binding TAT-1 Aminophospholipid Translocase
2011 (English)In: Traffic: the International Journal of Intracellular Transport, ISSN 1398-9219, E-ISSN 1600-0854, Vol. 12, no 12, 1839-1849 p.Article in journal (Refereed) Published
Numb regulates endocytosis in many metazoans, but the mechanism by which it functions is not completely understood. Here we report that the Caenorhabditis ele-gans 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.
Place, publisher, year, edition, pages
Malden: Wiley-Blackwell, 2011. Vol. 12, no 12, 1839-1849 p.
C. elegans, endocytosis, numb, phosphatidylserine, recycling, tat-1
IdentifiersURN: urn:nbn:se:umu:diva-50937DOI: 10.1111/j.1600-0854.2011.01271.xISI: 000297573500014PubMedID: 21917090OAI: oai:DiVA.org:umu-50937DiVA: diva2:473226