mBet3p is required for homotypic COPII vesicle tethering in mammalian cells (original) (raw)

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Article| July 31 2006

Sidney Yu,

1Howard Hughes Medical Institute

2Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519

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Ayano Satoh,

2Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519

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Marc Pypaert,

2Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519

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Karl Mullen,

3Division of Biological Sciences, The University of Montana, Missoula, MT 59812

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Jesse C. Hay,

3Division of Biological Sciences, The University of Montana, Missoula, MT 59812

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Susan Ferro-Novick

1Howard Hughes Medical Institute

2Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519

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Sidney Yu

1Howard Hughes Medical Institute

2Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519

Ayano Satoh

2Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519

Marc Pypaert

2Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519

Karl Mullen

3Division of Biological Sciences, The University of Montana, Missoula, MT 59812

Jesse C. Hay

3Division of Biological Sciences, The University of Montana, Missoula, MT 59812

Susan Ferro-Novick

1Howard Hughes Medical Institute

2Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06519

Abbreviations used in this paper: MVB, multivesicular body; tER, transitional ER; VTC, vesicular tubular cluster.

Received: March 09 2006

Accepted: June 23 2006

Online ISSN: 1540-8140

Print ISSN: 0021-9525

The Rockefeller University Press

2006

J Cell Biol (2006) 174 (3): 359–368.

TRAPPI is a large complex that mediates the tethering of COPII vesicles to the Golgi (heterotypic tethering) in the yeast Saccharomyces cerevisiae. In mammalian cells, COPII vesicles derived from the transitional endoplasmic reticulum (tER) do not tether directly to the Golgi, instead, they appear to tether to each other (homotypic tethering) to form vesicular tubular clusters (VTCs). We show that mammalian Bet3p (mBet3p), which is the most highly conserved TRAPP subunit, resides on the tER and adjacent VTCs. The inactivation of mBet3p results in the accumulation of cargo in membranes that colocalize with the COPII coat. Furthermore, using an assay that reconstitutes VTC biogenesis in vitro, we demonstrate that mBet3p is required for the tethering and fusion of COPII vesicles to each other. Consistent with the proposal that mBet3p is required for VTC biogenesis, we find that ERGIC-53 (VTC marker) and Golgi architecture are disrupted in siRNA-treated mBet3p-depleted cells. These findings imply that the TRAPPI complex is essential for VTC biogenesis.

The Rockefeller University Press

2006

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