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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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Rivera, V.M. et al.

Rivera, Wang, Wardwell, Courage, Volchuk, Keenan, Holt, Gilman, Orci, Cerasoli, Rothman, Clackson,

Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum.

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.[1]

References

Regulation of protein secretion through controlled aggregation in the endoplasmic reticulum. Rivera, V.M., Wang, X., Wardwell, S., Courage, N.L., Volchuk, A., Keenan, T., Holt, D.A., Gilman, M., Orci, L., Cerasoli, F., Rothman, J.E., Clackson, T. Science (2000) [Pubmed]

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