Enhancers: Holding Out for the Right Promoterby David S. Lorberbaum, Scott Barolo

Current Biology


New results from LEPS at SPring-8

Takashi Nakano, for the LEPS collaboration

The HOT study—further analyses

A Zanchetti for the study investigato

Hold it right there!

David Cockburn


proteins. J. Cell Biol. 208, 197–209. asparagine-linked oligosaccharide processing pathway. Glycobiology 4, 113–125. encoding alpha-glucosidase I is essential for degradation of malfolded glycoproteins of the endoplasmic reticulum. FEMS Yeast Res. 4, 815–820. the lumenal domain of Erv41p, a protein involved in transport between the endoplasmic 10203–10209. 17. Aoe, T., Lee, A.J., van Donselaar, E., Peters,

P.J., and Hsu, V.W. (1998). Modulation of intracellular transport by transported proteins: insight from regulation of COPI-mediated transport. Proc. Natl. Acad. Sci. USA 95, * gy o or r ho two kinds of genes. Most of our time is Differential gene expression, after all, istransport from the Golgi to the ER.

However, the precise mechanism for cargo release at the ER still needs to be studied inmore detail. Indeed, the authors show that a neutral pH is not sufficient to separate the cargo from the receptor, which suggests that additional unknown factors must be also involved in this process [5]. In addition, other interesting aspects remain to be addressed regarding the retrieval role of the

Erv41p–Erv46p complex, such as whether its retrograde trafficking is constitutive or regulated by cargo recognition, as seen with the KDEL receptor [17].

In addition to its role as a retrieval receptor, the Erv41p–Erv46p complex has recently been assigned another transport function. A new study by the Yoda lab [18] reports that the

Erv41p–Erv46p complex plays a role as an anterograde cargo receptor for the

Golgi mannosyltransferase Ktr4p during

ER export. Anterograde cargo receptors link newly synthesized secretory proteins to the COPII coat to facilitate their uptake into COPII vesicles for efficient transport to the Golgi. Like the retrieval receptors, they are also continuously cycling between the ER and Golgi and their receptor function has also been proposed to be regulated in a pH-dependent manner [1]. Further investigation will be required to understand how anterograde and retrograde cargo receptor activities can be coordinated to dynamically maintain the composition and functional homeostasis of the early secretory pathway.

REFERENCES 1. Dancourt, J., and Barlowe, C. (2010). Protein sorting receptors in the early secretory pathway. Annu. Rev. Biochem. 79, 777–802. 2. Munro, S., and Pelham, H.R. (1987).

A C-terminal signal prevents secretion of luminal ER proteins. Cell 48, 899–907. 3. Semenza, J.C., Hardwick, K.G., Dean, N., and

Pelham, H.R. (1990). ERD2, a yeast gene required for the receptor-mediated retrieval of luminal ER proteins from the secretory pathway. Cell 61, 1349–1357. 4. Sato, K., Sato, M., and Nakano, A. (1997).

Rer1p as common machinery for the endoplasmic reticulum localization of membrane proteins. Proc. Natl. Acad. Sci.

USA 94, 9693–9698. 5. Shibuya, A., Margulis, N., Christiano, R.,

Walther, T.C., and Barlowe, C. (2015). The

R290 Current Biology 25, R269–R293, March11. Frohlich, F., Christiano, R., and Walther, T.C. (2013). Native SILAC: metabolic labeling of proteins in prototroph microorganisms based on lysine synthesis regulation. Mol. Cell.

Proteomics 12, 1995–2005.

Enhancers: Holdin

Right Promoter

David S. Lorberbaum and Scott Barolo

Department of Cell and Developmental Biolo

Biology, University of Michigan Medical Scho *Correspondence: sbarolo@umich.edu http://dx.doi.org/10.1016/j.cub.2015.01.039

Some transcriptional enhancers w while ignoring others. How widesp genome? A new study finds that, in to activate promoters resembling t

To developmental biologists, there arespent thinking about what we might call the ‘interesting’ category, which covers all genes whose expression is differentially regulated — that is, genes that are more strongly expressed in cell A compared to 30, 2015 ª2015 Elsevier Ltd All rights reserved1624–1629. 18. Noda, Y., Hara, T., Ishii, M., and Yoda, K. (2014). Distinct adaptor proteins assist exit of

Kre2-family proteins from the yeast ER. Biol.

Open 3, 209–224. g Out for the and Program in Cellular and Molecular l, Ann Arbor, MI 48109, USA k best with one type of promoter, ead is such specificity across the a fair fight, most enhancers prefer se of their parent genes. cell B, or at stage X compared to stage Y.10. Hitt, R., and Wolf, D.H. (2004). DER7,6. Otte, S., Belden, W.J., Heidtman, M., Liu, J.,

Jensen, O.N., and Barlowe, C. (2001).

Erv41p and Erv46p: new components of

COPII vesicles involved in transport between the ER and Golgi complex. J. Cell Biol. 152, 503–518. 7. Otte, S., and Barlowe, C. (2002). The

Erv41p-Erv46p complex: multiple export signals are required in trans for COPII-dependent transport from the ER. EMBO J. 21, 6095–6104. 8. Welsh, L.M., Tong, A.H., Boone, C., Jensen,

O.N., and Otte, S. (2006). Genetic and molecular interactions of the Erv41p-Erv46p complex involved in transport between the endoplasmic reticulum and Golgi complex.

J. Cell Sci. 119, 4730–4740. 9. Moremen, K.W., Trimble, R.B., and

Herscovics, A. (1994). Glycosidases of the reticulum and Golgi apparatus. J. Mol. Biol. 425, 2208–2218. 13. Sandvig, K., and van Deurs, B. (2002).

Membrane traffic exploited by protein toxins.

Annu. Rev. Cell. Dev. Biol. 18, 1–24. 14. Paroutis, P., Touret, N., and Grinstein, S. (2004). The pH of the secretory pathway: measurement, determinants, and regulation.

Physiology 19, 207–215. 15. Llopis, J., McCaffery, J.M., Miyawaki, A.,

Farquhar, M.G., and Tsien, R.Y. (1998).

Measurement of cytosolic, mitochondrial, and

Golgi pH in single living cells with green fluorescent proteins. Proc. Natl. Acad. Sci.

USA 95, 6803–6808. 16. Scheel, A.A., and Pelham, H.R. (1996).

Purification and characterization of the human KDEL receptor. Biochemistry 35,Erv41p-Erv46p complex serves as a retrograde receptor to retrieve escaped ER12. Biterova, E.I., Svard, M., Possner, D.D., and

Guy, J.E. (2013). The crystal structure of

Current Biology

Dispatchesthe cornerstone of development and many other complex biological processes: it’s what makes a cell different from its neighbor. The second category— genes whose expression is consistent across cell types and developmental stages — receives the pejorative label of ‘housekeeping genes’, even though many dCP enhancers