Transcriptional regulation of secretory capacity by bZip transcription factors

Abstract

Cells of specialized secretory organs expand their secretory pathways to accommodate the increased protein load necessary for their function. The endoplasmic reticulum (ER), the Golgi apparatus and the secretory vesicles, expand not only the membrane components but also the protein machinery required for increased protein production and transport. Increased protein load causes an ER stress response akin to the Unfolded Protein Response (UPR). Recent work has implicated several bZip transcription factors in the regulation of protein components of the early secretory pathway necessary to alleviate this stress. Here, we highlight eight bZip transcription factors in regulating secretory pathway component genes. These include components of the three canonical branches of the UPR–ATF4, XBP1, and ATF6, as well as the five members of the Creb3 family of transcription factors. We review findings from both invertebrate and vertebrate model systems suggesting that all of these proteins increase secretory capacity in response to increased protein load. Finally, we propose that the Creb3 family of factors may have a dual role in secretory cell differentiation by also regulating the pathways necessary for cell cycle exit during terminal differentiation.

Keywords

bZip transcription factors / endoplasmic reticulum / Golgi / secretion / secretory capacity / secretory vesicles

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Acknowledgements

We thank Caitlin Hanlon, Rajprasad Loganathan and Carolyn Machamer for critical reading of this manuscript. Our work on the transcriptional regulation of secretory capacity is supported by NIH K99 DE021461 (R.M.F.) and NIH RO1 DE013899 (D.J.A.).

Rebecca M. Fox and Deborah J. Andrew declare that they have no conflict of interest.

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