title: The intracellular transport of chylomicrons requires the small GTPase, Sar1b.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, UK. carol.shoulders@csc.mrc.ac.uk
authors.forename: Carol C
authors.initials: CC
authors.lastname: Shoulders
authors.forename: David J
authors.initials: DJ
authors.lastname: Stephens
authors.forename: Bethan
authors.initials: B
authors.lastname: Jones
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001693:Biological Transport, Active; D002352:Carrier Proteins; D002914:Chylomicrons / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006011:Glycogen Storage Disease Type IV / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D010750:Phosphoproteins; D029701:Saccharomyces cerevisiae Proteins; D013132:Spinocerebellar Degenerations / Q000235:genetics / Q000378:metabolism; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D002914:Chylomicrons; D010750:Phosphoproteins; C106113:SEC31 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D033921:Vesicular Transport Proteins; C493083:SAR1A protein, human; C513282:SAR1B protein, human; D020559:Monomeric GTP-Binding Proteins