Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum - PubMed (original) (raw)

. 2000 Feb 4;287(5454):826-30.

doi: 10.1126/science.287.5454.826.

X Wang, S Wardwell, N L Courage, A Volchuk, T Keenan, D A Holt, M Gilman, L Orci, F Cerasoli Jr, J E Rothman, T Clackson

Affiliations

• PMID: 10657290
• DOI: 10.1126/science.287.5454.826

Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum

V M Rivera et al. Science. 2000.

Abstract

A system for direct pharmacologic control of protein secretion was developed to allow rapid and pulsatile delivery of therapeutic proteins. A protein was engineered so that it accumulated as aggregates in the endoplasmic reticulum. Secretion was then stimulated by a synthetic small-molecule drug that induces protein disaggregation. Rapid and transient secretion of growth hormone and insulin was achieved in vitro and in vivo. A regulated pulse of insulin secretion resulted in a transient correction of serum glucose concentrations in a mouse model of hyperglycemia. This approach may make gene therapy a viable method for delivery of polypeptides that require rapid and regulated delivery.

PubMed Disclaimer

Comment in

• Perspectives: drug delivery. Regulating export of ER cargo.
  Aridor M, Balch WE. Aridor M, et al. Science. 2000 Feb 4;287(5454):816-7. doi: 10.1126/science.287.5454.816. Science. 2000. PMID: 10691557 No abstract available.

Similar articles

• Perspectives: drug delivery. Regulating export of ER cargo.
  Aridor M, Balch WE. Aridor M, et al. Science. 2000 Feb 4;287(5454):816-7. doi: 10.1126/science.287.5454.816. Science. 2000. PMID: 10691557 No abstract available.
• Differentiation-induced insulin secretion from nonendocrine cells with engineered human proinsulin cDNA.
  Yamasaki K, Sasaki T, Nemoto M, Eto Y, Tajima N. Yamasaki K, et al. Biochem Biophys Res Commun. 1999 Nov 19;265(2):361-5. doi: 10.1006/bbrc.1999.1698. Biochem Biophys Res Commun. 1999. PMID: 10558872
• Insulin delivery with plasmid DNA.
  Abai AM, Hobart PM, Barnhart KM. Abai AM, et al. Hum Gene Ther. 1999 Nov 1;10(16):2637-49. doi: 10.1089/10430349950016672. Hum Gene Ther. 1999. PMID: 10566891
• A review on insulin trafficking and exocytosis.
  Vakilian M, Tahamtani Y, Ghaedi K. Vakilian M, et al. Gene. 2019 Jul 20;706:52-61. doi: 10.1016/j.gene.2019.04.063. Epub 2019 Apr 27. Gene. 2019. PMID: 31039435 Review.
• Insulin biosynthesis and secretion--a still unsettled topic.
  Renold AE. Renold AE. N Engl J Med. 1970 Jan 22;282(4):173-82. doi: 10.1056/NEJM197001222820401. N Engl J Med. 1970. PMID: 4311880 Review. No abstract available.

Cited by

• A Novel Frizzled-Based Screening Tool Identifies Genetic Modifiers of Planar Cell Polarity in Drosophila Wings.
  Carvajal-Gonzalez JM, Mulero-Navarro S, Smith M, Mlodzik M. Carvajal-Gonzalez JM, et al. G3 (Bethesda). 2016 Dec 7;6(12):3963-3973. doi: 10.1534/g3.116.035535. G3 (Bethesda). 2016. PMID: 27729438 Free PMC article.
• The clathrin adaptor AP-1 complex and Arf1 regulate planar cell polarity in vivo.
  Carvajal-Gonzalez JM, Balmer S, Mendoza M, Dussert A, Collu G, Roman AC, Weber U, Ciruna B, Mlodzik M. Carvajal-Gonzalez JM, et al. Nat Commun. 2015 Apr 7;6:6751. doi: 10.1038/ncomms7751. Nat Commun. 2015. PMID: 25849195 Free PMC article.
• Membrane trafficking in health and disease.
  Yarwood R, Hellicar J, Woodman PG, Lowe M. Yarwood R, et al. Dis Model Mech. 2020 Apr 30;13(4):dmm043448. doi: 10.1242/dmm.043448. Dis Model Mech. 2020. PMID: 32433026 Free PMC article. Review.
• Diversifying the secretory routes in neurons.
  Valenzuela JI, Perez F. Valenzuela JI, et al. Front Neurosci. 2015 Oct 7;9:358. doi: 10.3389/fnins.2015.00358. eCollection 2015. Front Neurosci. 2015. PMID: 26500481 Free PMC article. Review.
• zapERtrap: A light-regulated ER release system reveals unexpected neuronal trafficking pathways.
  Bourke AM, Schwartz SL, Bowen AB, Kleinjan MS, Winborn CS, Kareemo DJ, Gutnick A, Schwarz TL, Kennedy MJ. Bourke AM, et al. J Cell Biol. 2021 Sep 6;220(9):e202103186. doi: 10.1083/jcb.202103186. Epub 2021 Jul 9. J Cell Biol. 2021. PMID: 34241635 Free PMC article.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Atypon
  • Ovid Technologies, Inc.

• Other Literature Sources

  • The Lens - Patent Citations Database