CSFN PI Directory

Jesse Hay

Professor, DBS

Contact

Office
Health Science 302A
Phone
406-243-2381
Email
Jesse.Hay@umontana.edu

Education

Ph.D. University of Wisconsin-Madison, 1994
Postdoctoral Training, Stanford University, 1994-1998

Courses Taught

BIOB 425--Advanced Cellular & Molecular Biology

BIOH 458--Neuroscience Research Techniques

 

 

Research Interests

The secretory pathway employs vesicle transport to provide a linear pathway for export of cellular products and distribution of membrane and organelle components throughout the cytoplasm. Many diseases, including neurodegeneration, involve disruption of the biosynthetic secretory pathway and unresolved secretory stress–making it essential to understand how secretion is up- and down-regulated under different physiological conditions.  In mammals, ER-to-Golgi transport, which represents the rate-limiting step in the secretory pathway and the step most relevant to transport-related diseases, has been extensively characterized. In broad terms, ER-to-Golgi transport is initiated at ER exit sites (ERES) and involves cargo sorting and vesicle budding mediated by the COPII vesicle coat. We are trying to understand how these processes are adjusted dynamically to match secretory output rates with the needs to enforce secretory quality control, avoid ER stress, and keep pace with secretory protein biogenesis and cell growth. 

One key aspect to regulation of ER-to-Golgi transport that has become apparent in recent years is the role of ER luminal calcium. Calcium, when released from the ER, appears to interact with penta-EF hand proteins (PEFs) in the cytoplasm that bind to the COPII coat at ERES and modulate its assembly and the rate of cargo egress from the ER. Recent results from our lab indicate that PEF proteins can either up- or down-regulate ER export, depending upon the nature of the calcium signal and the sub-complexes that the PEF proteins form in response. Furthermore, PEF proteins seem to regulate the cargo selection process itself, helping to determine the balance between secretion and retention. We employ trafficking assays of ER-to-Golgi transport in live mammalian cell lines, live-cell calcium measurements, immunoprecipitations, and live-cell fluorescence microscopy of protein dynamics at ERES to learn how calcium, PEF proteins, and COPII components are integrated to dynamically regulate cargo sorting and retention decisions. This project for the first time outlines a robust regulatory network by which PEF proteins and Ca2+ throttle and damper ER cargo sorting to adapt the secretory pathway to current Ca2+ conditions, with significant physiological consequences. These studies will have wide significance because proper regulation of secretion is fundamental to cell function and survival during stresses. 

Field of Study

Molecular Cell Biology

Selected Publications

Dalu Xu, Ashwini Joglekar, Antionette L. Williams, and Jesse C. Hay. 2000. Subunit Structure of a Mammalian ER/Golgi SNARE Complex. Journal of Biological Chemistry 275:39631-39639.

Dalu Xu and Jesse C. Hay. 2004. In Vitro Reconstitution of Homotypic COPII Vesicle Fusion to Generate a Pre-Golgi Intermediate Compartment. Journal of Cell biology 167:997-1003.

Marvin Bentley, Yingjian Liang, Karl Mullen, Dalu Xu, Elizabeth Sztul, and Jesse C. Hay. 2006. SNARE Status Regulates Tether Recruitment and Function in Homotypic COPII Vesicle Fusion. Journal of Biological Chemistry 281:38825-38833.

Jesse C. Hay.  2007.  Calcium: a Fundamental Regulator of Membrane Fusion?  EMBO Reports 8:236-240.

Marvin Bentley, Deborah Nycz, Ashwini Joglekar, and Jesse C. Hay.  2010.  Vesicular Calcium Regulates Coat Retention, Fusogenicity and Size of Pre-Golgi Intermediates.  Molecular Biology of the Cell 21:1033-1046.

Nandhakumar Thayanidhi, Jared Helm, Deborah C. Nycz, Marvin Bentley, Yingjian Liang and Jesse C. Hay.  2010.  Alpha-Synuclein Delays Endoplasmic Reticulum (ER)-to-Golgi Transport in Mammalian Cells by Antagonizing ER/Golgi SNAREs.  Molecular Biology of the Cell 21:1850-1863.

Nandhakumar Thayanidhi, Yingjian Liang, Haruki Hasegawa, Deborah Nycz, Viola Oorschot, Judith Klumperman, and Jesse C. Hay.  2012.  R-SNARE YKT6 Resides in Membrane-Associated Protease-Resistant Protein Particles and Modulates Cell Cycle Progression When Over-Expressed.  Biology of the Cell 104:397-417.

Meg Trahey, Hyung Suk Oh, Craig E. Cameron, and Jesse C. Hay.  2012.  Poliovirus Infection Transiently Increases COPII Vesicle Budding.  Journal of Virology 86:9675-9682.

J. Helm, M. Bentley, K. Thorsen, T. Wang, L. Foltz, J. Klumperman,  J. C. Hay.  2014.  Apoptosis-linked Gene-2/Sec31 Interactions Regulate ER-to-Golgi Transport: a Potential Effector Pathway for Luminal Calcium. Journal of Biological Chemistry 289:23609-28.

Ting Wang, Robert Grabski, Elizabeth Sztul and Jesse C. Hay.  2015.  P115-SNARE interactions: a dynamic cycle of P115 binding monomeric SNARE motifs and releasing assembled bundles.  Traffic 16:148–171.

Ting Wang and Jesse C. Hay.  2015.  Alpha-synuclein Toxicity in the Early Secretory Pathway: How It Drives Neurodegeneration in Parkinsons Disease. Frontiers Neuroscience 9:433.

Mariah Rayl, Mishana Truitt, Aaron Held, John Sargeant, Kevin Thorsen, and Jesse C. Hay.  2016.  Peflin is a Negative Regulator of ER-to-Golgi Transport.  PLoS one, 11(6):e0157227.

Depaoli, M., Hay, J., Graier, W., Malli, R.  2019.  The enigmatic ATP supply of the endoplasmic reticulum.  Biol. Rev. 94:610-628.

Bischof, H., Hay, J., Graier, W., Malli, R.  2020.  ER-to-Golgi transport in HeLa cells displays high resilience to Ca2+  and energy stresses. Cells 9:2311.

Parashar, S., Chidambaram, R., Chen, S., Liem, C. R., Griffis, E., Lambert, G. G., Shaner, N. C., Wortham, M., Hay, J. C., and Ferro-Novick, S.  2021.  Endoplasmic reticulum tubules limit the size of misfolded protein condensates. Elife 10:e71642.

Sargeant, J., Seiler, D. K., Costain, T., Madreiter-Sokolowski, C. T., Gordon, D. E., Peden, A. A., Malli, R., Graier, W. F. and Hay, J. C.  2021.  ALG-2 and peflin regulate COPII targeting and secretion in response to calcium signaling.  J Biol Chem 297(6):101393.

Sargeant, J., and Hay, J. C. 2022. Ca2+ regulation of constitutive vesicle trafficking. Faculty Reviews 11:6.

Seiler, D. K., and Hay, J. C. 2022. Genetically encoded fluorescent tools: Shining a little light on ER-to-Golgi transport. Free Radical Biology and Medicine 183:14–24.

Held, A., Lapka, J., Sargeant, J., Hojanazarova, J., Madreiter-Sokolowski, C., Malli, R., Graier, W. F., and Hay, J. C. 2023. Steady-state regulation of COPII-dependent secretory cargo sorting by inositol trisphosphate receptors, calcium, and penta EF hand proteins. J. Biol Chem. https://doi.org/10.1016/j.jbc.2023.105471.