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Caenorhabditis elegans Numb Inhibits Endocytic Recycling by Binding TAT-1 Aminophospholipid Translocase
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). (Simon Tuck)
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). (Simon Tuck)
Umeå University, Faculty of Medicine, Umeå Centre for Molecular Medicine (UCMM). (Simon Tuck)
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
Abstract [en]

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.
Keyword [en]
C. elegans, endocytosis, numb, phosphatidylserine, recycling, tat-1
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:umu:diva-50937DOI: 10.1111/j.1600-0854.2011.01271.xISI: 000297573500014PubMedID: 21917090OAI: oai:DiVA.org:umu-50937DiVA: diva2:473226
Available from: 2012-01-05 Created: 2012-01-02 Last updated: 2017-12-08Bibliographically approved

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