title: Lumenal protein sorting to the constitutive secretory pathway of a regulated secretory cell.
abstract: Newly synthesized secretory granule content proteins are delivered via the Golgi complex for storage within mature granules, whereas constitutive secretory proteins are not stored. Most soluble proteins traveling anterograde through the trans-Golgi network are not excluded from entering immature secretory granules, whether or not they have granule-targeting signals. However, the ;sorting-for-entry' hypothesis suggests that soluble lumenal proteins lacking signals enter transport intermediates for the constitutive secretory pathway. We aimed to investigate how these constitutive secretory proteins are sorted. In a pancreatic beta-cell line, we stably expressed two lumenal proteins whose normal sorting information has been deleted: alkaline phosphatase, truncated to eliminate its glycosylphosphatidylinositol membrane anchor (SEAP); and Cab45361, a Golgi lumenal resident, truncated to eliminate its intracellular retention (Cab308Myc). Both truncated proteins are efficiently secreted, but whereas SEAP enters secretory granules, Cab308Myc behaves as a true constitutive marker excluded from granules. Interestingly, upon permeabilization of organelle membranes with saponin, SEAP is extracted as a soluble protein whereas Cab308Myc remains associated with the membrane. These are among the first data to support a model in which association with the lumenal aspect of Golgi and/or post-Golgi membranes can serve as a means for selective sorting of constitutive secretory proteins.
authors.affiliation: Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Lara-Lemus
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.forename: Mark D
authors.initials: MD
authors.lastname: Turner
authors.forename: Philipp
authors.initials: P
authors.lastname: Scherer
authors.forename: Gudrun
authors.initials: G
authors.lastname: Stenbeck
authors.forename: Puneeth
authors.initials: P
authors.lastname: Iyengar
authors.forename: Peter
authors.initials: P
authors.lastname: Arvan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037281:Calnexin / Q000378:metabolism; D002460:Cell Line; D006023:Glycoproteins / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D021382:Protein Sorting Signals; D021381:Protein Transport / Q000502:physiology*; D051381:Rats
chemical_list: D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D007328:Insulin; D021382:Protein Sorting Signals; D037281:Calnexin; D000469:Alkaline Phosphatase