Genetics and molecular biologyThe intracellular transport of chylomicrons requires the small GTPase, Sar1bShoulders, Carol Ca; Stephens, David Jb; Jones, BethanaAuthor Information aMedical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, UK; and bDepartment of Biochemistry, University of Bristol, School of Medical Sciences, Bristol, UK Correspondence to Carol C. Shoulders, MRC Clinical Sciences Centre, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK Tel: +44 020 8383 4318; fax: +44 020 8383 2028; e-mail: [email protected] Abbreviations CMRD: chylomicron retention disease ER: endoplasmic reticulum ERES: endoplasmic reticulum exit site GDP: guanosine diphosphate GTP: guanosine triphosphate MSS: Marinesco-Sjögren syndrome VSV-G: vesicular stomatitis virus Current Opinion in Lipidology: April 2004 - Volume 15 - Issue 2 - p 191-197 Buy Abstract Purpose of review The transport of lipoproteins through the secretory pathways of enterocytes and hepatocytes is pivotal for whole-body lipid homeostasis. This review focuses on the assembly and structural evolution of COPII (coat protein) transport carriers that are essential for the transport of chylomicrons from the endoplasmic reticulum to the Golgi apparatus. Recent findings The assembly of endoplasmic reticulum to Golgi transport carriers commences with the coating of specific areas of the endoplasmic reticulum membrane with Sar1-GTP and the Sec23/24 heterodimer. An important advance has been the crystallographic analysis of the Sar1-Sec23/24 complex. The proteins form a bow-tie shaped structure, with a concave face that seems to match the curvature of transport carriers. Mammalian cells produce two isoforms of Sar1, designated Sar1a and Sar1b, both of which are expressed in enterocytes. Sar1b is defective in chylomicron retention disease and Anderson disease, two rare recessive disorders characterized by severe fat malabsorption and a failure to thrive in infancy. Patients with chylomicron retention disease and Anderson disease selectively retain chylomicron-like particles within membrane-bound compartments. By analogy with procollagen, chylomicrons may drive the formation of endoplasmic reticulum to Golgi transport carriers from endoplasmic reticulum sites close to, but separate from, domains of the endoplasmic reticulum coated with Sar1-Sec23/24. The COPII machinery also mediates the transport of VLDL to the Golgi. Summary New insights into the role of the COPII machinery in the intracellular transport of cargo, including chylomicrons and VLDL, may suggest new drug targets for ameliorating the lipid abnormalities of the metabolic syndrome. © 2004 Lippincott Williams & Wilkins, Inc.