Regulation of protein compartmentalization expands the diversity of protein function

Kelly L. Shaffer, Ajay Sharma, Erik L. Snapp, Ramanujan S. Hegde

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)545-554
Number of pages10
JournalDevelopmental Cell
Volume9
Issue number4
DOIs
StatePublished - Oct 2005

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Calreticulin
Protein Sorting Signals
Endoplasmic Reticulum
Proteins
Glucocorticoid Receptors
Accessories
Secretory Pathway
Protein Transport
Genes
Cytosol
Chemical activation
Transcriptional Activation
Membranes

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Regulation of protein compartmentalization expands the diversity of protein function. / Shaffer, Kelly L.; Sharma, Ajay; Snapp, Erik L.; Hegde, Ramanujan S.

In: Developmental Cell, Vol. 9, No. 4, 10.2005, p. 545-554.

Research output: Contribution to journalArticle

Shaffer, Kelly L. ; Sharma, Ajay ; Snapp, Erik L. ; Hegde, Ramanujan S. / Regulation of protein compartmentalization expands the diversity of protein function. In: Developmental Cell. 2005 ; Vol. 9, No. 4. pp. 545-554.
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