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Letter

Nature 439, 604-607 (2 February 2006) | doi:10.1038/nature04377; Received 22 August 2005; Accepted 18 October 2005

Functional genomics reveals genes involved in protein secretion and Golgi organization

Frederic Bard1, Laetitia Casano1, Arrate Mallabiabarrena1, Erin Wallace1, Kota Saito1, Hitoshi Kitayama1, Gianni Guizzunti1, Yue Hu1, Franz Wendler2, Ramanuj DasGupta3, Norbert Perrimon3 & Vivek Malhotra1

  1. Cell and Developmental Biology Department, University of California San Diego, La Jolla, California 92093-0634, USA
  2. National Institute for Medical Research, the Ridgeway Mill Hill, London NW7 1AA, UK
  3. Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA

Correspondence to: Vivek Malhotra1 Correspondence and requests for materials should be addressed to V.M. (Email: malhotra@biomail.ucsd.edu).

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Yeast genetics and in vitro biochemical analysis have identified numerous genes involved in protein secretion1, 2. As compared with yeast, however, the metazoan secretory pathway is more complex and many mechanisms that regulate organization of the Golgi apparatus remain poorly characterized. We performed a genome-wide RNA-mediated interference screen in a Drosophila cell line to identify genes required for constitutive protein secretion. We then classified the genes on the basis of the effect of their depletion on organization of the Golgi membranes. Here we show that depletion of class A genes redistributes Golgi membranes into the endoplasmic reticulum, depletion of class B genes leads to Golgi fragmentation, depletion of class C genes leads to aggregation of Golgi membranes, and depletion of class D genes causes no obvious change. Of the 20 new gene products characterized so far, several localize to the Golgi membranes and the endoplasmic reticulum.