Cis and trans interactions between atlastin molecules during membrane fusion.

Liu, Tina Y; Bian, Xin; Romano, Fabian B; Shemesh, Tom; Rapoport, Tom A; Hu, Junjie

Liu, Tina Y; Bian, Xin; Romano, Fabian B; Shemesh, Tom; Rapoport, Tom A; Hu, Junjie.

Afiliación

Liu TY; Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
Bian X; Tianjin Key Laboratory of Protein Sciences, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin 300071, China;
Romano FB; Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115;
Shemesh T; Faculty of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel; and.
Rapoport TA; Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115; tom_rapoport@hms.harvard.edu.
Hu J; Tianjin Key Laboratory of Protein Sciences, Department of Genetics and Cell Biology, College of Life Sciences, Nankai University, Tianjin 300071, China; National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Science, Beijing 100101, China.

Proc Natl Acad Sci U S A ; 112(15): E1851-60, 2015 Apr 14.

Article en En | MEDLINE | ID: mdl-25825753

RESUMEN

Atlastin (ATL), a membrane-anchored GTPase that mediates homotypic fusion of endoplasmic reticulum (ER) membranes, is required for formation of the tubular network of the peripheral ER. How exactly ATL mediates membrane fusion is only poorly understood. Here we show that fusion is preceded by the transient tethering of ATL-containing vesicles caused by the dimerization of ATL molecules in opposing membranes. Tethering requires GTP hydrolysis, not just GTP binding, because the two ATL molecules are pulled together most strongly in the transition state of GTP hydrolysis. Most tethering events are futile, so that multiple rounds of GTP hydrolysis are required for successful fusion. Supported lipid bilayer experiments show that ATL molecules sitting on the same (cis) membrane can also undergo nucleotide-dependent dimerization. These results suggest that GTP hydrolysis is required to dissociate cis dimers, generating a pool of ATL monomers that can dimerize with molecules on a different (trans) membrane. In addition, tethering and fusion require the cooperation of multiple ATL molecules in each membrane. We propose a comprehensive model for ATL-mediated fusion that takes into account futile tethering and competition between cis and trans interactions.

Asunto(s)

Proteínas de Drosophila/metabolismo; GTP Fosfohidrolasas/metabolismo; Fusión de Membrana; Proteínas de la Membrana/metabolismo; Vesículas Transportadoras/metabolismo; Algoritmos; Animales; Proteínas de Drosophila/química; Proteínas de Drosophila/genética; Drosophila melanogaster/genética; Drosophila melanogaster/metabolismo; Transferencia Resonante de Energía de Fluorescencia; GTP Fosfohidrolasas/química; GTP Fosfohidrolasas/genética; Guanosina Trifosfato/metabolismo; Hidrólisis; Membrana Dobles de Lípidos/química; Membrana Dobles de Lípidos/metabolismo; Proteínas de la Membrana/química; Proteínas de la Membrana/genética; Microscopía Confocal; Microscopía Fluorescente; Modelos Biológicos; Modelos Moleculares; Mutación; Unión Proteica; Multimerización de Proteína; Estructura Terciaria de Proteína; Imagen de Lapso de Tiempo; Vesículas Transportadoras/química

Palabras clave

GTPase; endoplasmic reticulum; lipid bilayer; membrane docking; spastic paraplegia type 3A gene

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vesículas Transportadoras / Proteínas de Drosophila / GTP Fosfohidrolasas / Fusión de Membrana / Proteínas de la Membrana Límite: Animals Idioma: En Revista: Proc Natl Acad Sci U S A Año: 2015 Tipo del documento: Article Pais de publicación: Estados Unidos

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