Hoyer Laboratory

Neuronal Organelle Quality Control and Health

Eliminating specific protein targets or even entire cellular organelles is important for generating and maintaining healthy neurons. The Hoyer Lab aims to understand how neurodegenerative diseases can be prevented by improving these key quality control mechanisms. Our target organelle is the endoplasmic reticulum (ER), which is essential to neuronal connectivity. The ER network has many important functions such as providing a site for protein synthesis, storing and releasing calcium for signaling, and forming regulatory membrane contact sites with other organelles. Importantly, impaired ER network formation or defective ER clearance mechanisms are linked to neurological disorders.

The Hoyer Lab characterizes ER surveillance mechanisms at the molecular level by combining genetic manipulation of stem cells, which can be efficiently converted to different neuronal cell populations. The lab employs various investigative approaches including quantitative proteomics, live cell fluorescence microscopy, high resolution cryo-electron tomography and other biochemical techniques.

Our research covers three main areas with the goal of understanding ER quality control and function in neurons:

• Characterize upstream signals, molecular machinery, and spatio-temporal properties of ER removal through selective autophagy (“ER-phagy”) or other ER protein clearance mechanisms.
• Study the consequences of disrupted ER proteins levels in different types of neuronal cell types.
• Analyze ER proteins directly related to neurological disorders by performing systematic genetic modifications and quantitative proteomics.

Featured Publications

*Indicates equal contributions

Hoyer MJ, Smith IR, Paoli, JC, Jiang, Y, Paulo JA, Harper JW. 2024. Combinatorial selective ER-phagy remodels the ER during neurogenesis. Nat Cell Biol 26:378–392.

Eapen V*, Swarup S*, Hoyer MJ*, Paulo J, Harper JW. 2021. Quantitative proteomics reveals the selectivity of ubiquitin-binding autophagy receptors in the turnover of damaged lysosomes by lysophagy. eLife 10:e72328

Westrate LM*, Hoyer MJ*, Nash MJ, Voeltz GK. 2020. Vesicular and uncoated Rab1-dependent cargo carriers facilitate ER to Golgi transport. J Cell Sci 133(14).

Hoyer MJ, Chitwood PJ, Ebmeier, CC, Striepen, JF, Qi, RZ, Old WM, Voeltz GK. 2018. A novel class of ER membrane proteins regulates ER-associated endosome fission. Cell 175: 254–265.e14.

Rowland AA*, Chitwood PJ*, Phillips MJ+, Voeltz GK. 2014. ER contact sites define the position and timing of endosome fission. Cell 159:1027–1041.
+ Denotes previous name

Hoyer MJ, Harper, JW. 2023. ER membrane curvature and ubiquitin as drivers of ER-phagy. Dev Cell Spot 58(14):1219–1220.

Hoyer MJ, Swarup S, Harper JW. 2022. Mechanisms controlling selective elimination of damaged lysosomes. Curr Opin Physiol 29:100590

Salvador-Gallego R, Hoyer MJ, Voeltz GK. 2017. SnapShot: Functions of endoplasmic reticulum membrane contact sites. Cell 171:1224–1224.e1

Phillips MJ+, Voeltz GK. 2016. Structure and function of ER membrane contact sites with other organelles. Nat Rev Mol Cell Biol 1–14.
+ Denotes previous name