Regulation of protein compartmentalization expands the diversity of protein function.

Proteins destined for the secretory pathway are translocated into the endoplasmic reticulum (ER) by signal sequences that vary widely in their functional properties. We have investigated whether differences in signal sequence function have been exploited for cellular benefit. A cytosolic form of the ER chaperone calreticulin was found to arise by an aborted translocation mechanism dependent on its signal sequence and factors in the ER lumen and membrane. A signal sequence that functions independently of these accessory translocation factors selectively eliminated cytosolic calreticulin. In vivo replacement of endogenous calreticulin with a constitutively translocated form influenced glucocorticoid receptor-mediated gene activation without compromising chaperone activity in the ER. Thus, in addition to its well-established ER lumenal functions, calreticulin has an independent role in the cytosol that depends critically on its inefficient compartmentalization. We propose that regulation of protein translocation represents a potentially general mechanism for generating diversity of protein function.

Are There Missed Opportunities to Maximize Organ Donation Registrations? An Examination of Driver's License Applications Across the United States.

INTRODUCTION: With 116 000 people waiting for transplants and 8000 patients dying annually on waiting lists, the United States has a considerable organ shortage. An insufficient number of Americans have registered to become organ donors when obtaining driver's licenses or ID cards. Across states, there is considerable variability in organ donor registration rates as well as driver's license applications. METHODS: The purpose of this project was to describe the variability in the phrasing of the organ donor registration question by state bureaus of motor vehicles as well as other application questions that might influence this decision. In particular, the frequency of states employing empirically supported messages to increase donor registrations was ascertained. The content and phrasing of 46 different driver's license applications was coded in regard to seeking organ donor registrations. FINDINGS: No states used the empirically supported strategies of reciprocity, descriptive norms, or loss/gain framing from the interdisciplinary field of behavioral economics. Twelve states used injunctive norms to signify social approval for organ donation. Many state applications had lengthy organ donation sections and health questions that could discourage donor registrations. DISCUSSION: There is an extremely low use of empirically supported messages to increase organ donation registrations in driver's license applications in the United States. Opportunities exist for thoughtful consideration of the wording of driver's license applications. States interested in exploring ways to increase donations could undertake controlled variation of applications to test the effects of message framing on registration rates.