Publication in detail

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 2013 May 31. [Epub ahead of print]

Stress-inducible phosphoprotein 1 has unique cochaperone activity during development and regulates cellular response to ischemia via the prion protein.

Beraldo, FH; Soares, IN; Goncalves, DF; Fan, J; Thomas, AA; Santos, TG; Mohammad, AH; Roffé, M; Calder, MD; Nikolova, S; Hajj, GN; Guimaraes, AL; Massensini, AR; Welch, I; Betts, DH; Gros, R; Drangova, M; Watson, AJ; Bartha, R; Prado, VF; Martins, VR; Prado, MA

Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.

Abstract:
Stress-inducible phosphoprotein 1 (STI1) is part of the chaperone machinery, but it also functions as an extracellular ligand for the prion protein. However, the physiological relevance of these STI1 activities in vivo is unknown. Here, we show that in the absence of embryonic STI1, several Hsp90 client proteins are decreased by 50%, although Hsp90 levels are unaffected. Mutant STI1 mice showed increased caspase-3 activation and 50% impairment in cellular proliferation. Moreover, placental disruption and lack of cellular viability were linked to embryonic death by E10.5 in STI1-mutant mice. Rescue of embryonic lethality in these mutants, by transgenic expression of the STI1 gene, supported a unique role for STI1 during embryonic development. The response of STI1 haploinsufficient mice to cellular stress seemed compromised, and mutant mice showed increased vulnerability to ischemic insult. At the cellular level, ischemia increased the secretion of STI1 from wild-type astrocytes by 3-fold, whereas STI1 haploinsufficient mice secreted half as much STI1. Interesting, extracellular STI1 prevented ischemia-mediated neuronal death in a prion protein-dependent way. Our study reveals essential roles for intracellular and extracellular STI1 in cellular resilience.-Beraldo, F. H., Soares, I. N., Goncalves, D. F., Fan, J., Thomas, A. A., Santos, T. G., Mohammad, A. H., Roffe, M., Calder, M. D., Nikolova, S., Hajj, G. N., Guimaraes, A. N., Massensini, A. R., Welch, I., Betts, D. H., Gros, R., Drangova, M., Watson, A. J., Bartha, R., Prado, V. F., Martins, V. R., and Prado, M. A. M. Stress-inducible phosphoprotein 1 has unique cochaperone activity during development and regulates cellular response to ischemia via the prion protein.

» Online Version

Proven Track Record

The team at Ozgene has over two decades of experience creating customised knockout and knock-in mice for pivotal medical research globally. Over 300 scientific publications are based on research using Ozgene mice.

Go to Publications

Global Client Base

Ozgene generates genetically customised mice for researchers around the world. Ozgene mice can be found in 31 different countries on 5 continents from small academic institutions to multinational pharmaceutical companies.

See Map

Lean Management

Ozgene is applying Lean Management principles to deliver the highest quality services and shortest lead times to our customers. The implementation of Lean Culture has already seen an improvement in our processes and timelines.

Read More