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Review
. 2023 Jul 6:10:1197921.
doi: 10.3389/fmolb.2023.1197921. eCollection 2023.

Ubiquitin-mediated degradation at the Golgi apparatus

Lana Buzuk  1 , Doris Hellerschmied  1
Affiliations
Review

Ubiquitin-mediated degradation at the Golgi apparatus

Lana Buzuk et al. Front Mol Biosci. .

Abstract

The Golgi apparatus is an essential organelle of the secretory pathway in eukaryotic cells. It processes secretory and transmembrane proteins and orchestrates their transport to other endomembrane compartments or the plasma membrane. The Golgi apparatus thereby shapes the cell surface, controlling cell polarity, cell-cell communication, and immune signaling. The cytosolic face of the Golgi hosts and regulates signaling cascades, impacting most notably the DNA damage response and mitosis. These essential functions strongly depend on Golgi protein homeostasis and Golgi integrity. Golgi fragmentation and consequent malfunction is associated with neurodegenerative diseases and certain cancer types. Recent studies provide first insight into the critical role of ubiquitin signaling in maintaining Golgi integrity and in Golgi protein quality control. Similar to well described pathways at the endoplasmic reticulum, ubiquitin-dependent degradation of non-native proteins prevents the accumulation of toxic protein aggregates at the Golgi. Moreover, ubiquitination regulates Golgi structural rearrangements in response to cellular stress. Advances in elucidating ubiquitination and degradation events at the Golgi are starting to paint a picture of the molecular machinery underlying Golgi (protein) homeostasis.

Keywords: Golgi fragmentation; Golgi homeostasis; Golgi protein quality control; PROTAC; transmembrane protein degradation; ubiquitin E3 ligase; ubiquitin-mediated protein degradation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) Outline of a Golgi stack. (B) Cartoon model of the Dsc complex in yeast targeting substrates for ESCRT- and EGAD-mediated degradation. Non-native proteins recognized by the Dsc complex are shown in blue (ESCRT substrates) and purple (EGAD substrates). Dark blue and red stars indicate folding lesions within the TM domains of the substrate proteins. The Tul1 ubiquitinated ESCRT substrates are sorted into ILVs by the ESCRT machinery (not shown for simplicity). MVBs containing the ILVs fuse with the lysosome/vacuole and ubiquitinated proteins are degraded. The Tul1 ubiquitinated EGAD substrates are removed from the Golgi membrane and unfolded by Cdc48, and eventually degraded by the proteasome. (C) Current outline of E3 ligase-substrate pairs at the Golgi apparatus in mammalian cells. Selected E3 ligases (shown in brown) with their known substrates, where the ubiquitinated proteins can be targeted for degradation (shown in blue) or induce changes in protein-protein interactions (shown in yellow). The consequences of protein ubiquitination at the Golgi are stated in the text above.
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Grants and funding

This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)—SFB1430—Project-ID 424228829 and the Sofja Kovaleveskaja Award by the Alexander von Humboldt Foundation endowed by the Federal Ministry of Education and Research. We thank the International Max Planck Research School for Living Matter for continuous support.

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