Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2019 Dec;31(12):2833-2854.
doi: 10.1105/tpc.19.00433. Epub 2019 Oct 18.

Remove, Recycle, Degrade: Regulating Plasma Membrane Protein Accumulation

Cecilia Rodriguez-Furlan  1 , Elena A Minina  2   3 , Glenn R Hicks  4   2
Affiliations
Review

Remove, Recycle, Degrade: Regulating Plasma Membrane Protein Accumulation

Cecilia Rodriguez-Furlan et al. Plant Cell. 2019 Dec.

Abstract

Interactions between plant cells and the environment rely on modulation of protein receptors, transporters, channels, and lipids at the plasma membrane (PM) to facilitate intercellular communication, nutrient uptake, environmental sensing, and directional growth. These functions are fine-tuned by cellular pathways maintaining or reducing particular proteins at the PM. Proteins are endocytosed, and their fate is decided between recycling and degradation to modulate localization, abundance, and activity. Selective autophagy is another pathway regulating PM protein accumulation in response to specific conditions or developmental signals. The mechanisms regulating recycling, degradation, and autophagy have been studied extensively, yet we are just now addressing their regulation and coordination. Here, we (1) provide context concerning regulation of protein accumulation, recycling, or degradation by overviewing endomembrane trafficking; (2) discuss pathways regulating recycling and degradation in terms of cellular roles and cargoes; (3) review plant selective autophagy and its physiological significance; (4) focus on two decision-making mechanisms: regulation of recycling versus degradation of PM proteins and coordination between autophagy and vacuolar degradation; and (5) identify future challenges.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
PM Proteins: To Degrade or Not to Degrade? (A) Many PM proteins are constitutively endocytosed to maintain an active pool of proteins. Once they are endocytosed, they travel to the TGN/EE were they are recycled back to the PM by exocytosis. (B) Environmental or endogenous signals can trigger ubiquitination (Ub) of proteins that are then endocytosed by clathrin-dependent or -independent pathways. Proteins can be directed for degradation or deubiquitinated and returned to the recycling pathways (broken arrows). Proteins that continue through the degradation pathway are sorted at the TGN where LEs emerge. LEs mature by forming ILVs and become MVBs. At MVBs, proteins can be sent to the TGN/EE for recycling and saved from degradation. Alternatively, MBVs carrying proteins for degradation will fuse with the plant lytic compartment, the vacuole. (C) Under stress conditions, proteins at the PM can be degraded by autophagy. Autophagy can be nonselective or selective. During selective autophagy, the cargo to be internalized is either ubiquitin dependent (solid arrow) or ubiquitin independently tagged (broken arrow). Material selectively internalized is sequestered in a phagophore that matures into an autophagosome that will also fuse with the vacuole for degradation.
Figure 2.
Figure 2.
Endosome Maturation: RAB Conversion and Phosphoinositols. Endocytosed vesicles enriched in PtdIns(4)P arrive at the TGN/EE. Subdomains of the TGN/EE become decorated by PtdIns(3)P and RAB5-like proteins. RAB5-like endosomes detach from the TGN/EE (these endosomes are MVBs as they are described to have ILVs). RAB5-like endosomes are also enriched in PtdIns(3)P. VPS9 acts as a GEF exchanging GDP for GTP, activating the RAB5-like GTPases. RAB5-GTP then triggers the fusion of MVBs with the vacuole. Alternatively, RAB5-GTP can bind the complex MON1-CCZ1 that catalyzes GTP hydrolysis and RAB5-GDP exchange for RAB7-GDP. The MON1-CCZ1 complex also acts as a GEF for RAB7-like exchanging GDP for GTP. RAB7-like activated (GTP bound) can now trigger the fusion of the MVB to the vacuole. RAB5 and RAB7-like proteins are anchored to the membrane via a prenylated tail (black line).
Figure 3.
Figure 3.
Endosome Maturation: An ESCRT Point of View. ESCRTs are multi-subunit complexes that act sequentially through the endocytic pathway, directing ubiquitinated proteins into ILVs at LEs. Plants do not have a conventional ESCRT-0 complex; instead, TOL and SH3P2 proteins appear to fulfill this function. Sorting of ubiquitinated cargo proteins is proposed to start at the PM or right after endocytosis at the TGN/EE. Both TOL and SH3P2 directly interact with ubiquitin and clathrin. SH3P2 then can interacts with the ESCRT-I component FYVE/FREE1 that is anchored at the TGN/EE by PtdIns(3)P. FVYEE interacts with another ESCRT-I component, VPS23, and together they bind to ubiquitinated cargo continuing the sorting process. VPS23 binds to VPS27 and VPS28 assembling the entire ESCRT-I complex. The transition between ESCRT-I and ESCRT-II is still unclear in plants (broken arrow). However, the ESCRT-II subunit VPS36 binds ubiquitinated cargo, and the rest of the complex, namely, VPS22 and VPS25. ESCRT-II acts by clustering ubiquitinated cargo. The ESCRT-II VPS22 subunit then recruits the ESCRT-III VPS20 subunit at sites of ubiquitin cargo enrichment. VPS20 coordinates polymerization of SNF7/VPS24 into highly curved rings that sequester proteins forming ILV. AMSH3 protein acts by de-ubiquitinating cargo. Finally, the accessory proteins CHMP1, CHMP5 and IST1 regulate VPS4/SKD1-LIP5 ATPase complex activity to trigger the disassembly of the ESCRT complex. RAB5-like endosomes already present in ILV become an indicator of LE maturity.
Figure 4.
Figure 4.
Tether to Fuse: LEs to Vacuole. (A) to (C) Fusion of MVBs with the vacuole is facilitated by two tethering complexes CORVET (A) and HOPS (B). Core subunits VPS33, VPS16, VPS18, and VPS11 are part of both complexes. CORVET has two specific subunits, VPS8 and VPS3. In yeast, both VPS8 and VPS3 bind RAB5-like GTPases (arrows). In plants, VPS8 has proven to bind the plant RABF family members (solid arrow), while VPS3 remains to be tested (broken arrow). The HOPS complex also has two specific subunits, VPS41 and VPS39. In yeast, VP39 binds to a RAB7-like protein located at endosomes and VPS41 to another RAB7-like protein located at the vacuole (arrows). In plants, VPS39 has been characterized to bind RABG family (solid arrow), while VPS41 association to RAB7 remains to be tested (broken arrow). VPS33 from both subunits interacts with SNARE proteins. CORVET and HOPS act at different endosome populations connecting opposite membranes. CORVET interacts with the R-SNARE VAMP727 and with the Qa-SNARE SYP22, favoring the formation of a four-subunit oligomeric SNARE complex allowing fusion (see [C], top). Similarly, HOPS interacts with VAMP713 and VPS22, allowing formation of the fusion complex (see [C], bottom).
Figure 5.
Figure 5.
Recycling Retromers. (A) SNXs are believed to act by retrieving proteins for recycling at the TGN/EE and at RAB5-like endosomes. It is still debated whether SNX1 also acts at RAB7-like endosomes. The core retromer is anchored to RAB7-like endosomes and acts by recycling proteins before fusion with the vacuole. Proteins selected for retrieval by endosomes can be de-ubiquitinated by AMSH3. This de-ubiquitinating enzyme acts at the TGN/EE and at MBVs before the assembly of the ESCRT-III complex. Proteins are identified by colors as in (B) and (C). (B) The core retromer is anchored to MBVs by direct interaction of subunit VPS35 with RAB7-like proteins (RABG3f). The rest of the complex is then assembled by recruiting VPS26 and VPS29. (C) SNX1 can bind PtdIns(3)P by its PX domain, which anchors the protein to endosomal membranes (TGN/EE; MVBs). SNX1 can form homodimers or heterodimers when interacting with SNX2 through their BAR domains. SNX1 can also interact with CLASP-1, a plus-end microtubule (MT +) binding protein directing endosomes to the cell edges. SNX1 alternatively can interact with BLOC-1, which inhibits protein recycling. AMSH3, ASSOCIATED MOLECULE with the SH3 DOMAIN of STAM 3; BAR, Bin/Amphiphysin/Rvs domain; CLASP, MICROTUBULE-ASSOCIATED PROTEIN CYTOPLASMIC LINKER-ASSOCIATED PROTEINS; MT+, plus end microtubules; MVB, Multivesicular Bodies; PtdIns(3)P, phosphatidylinositol 3-phosphate; PX, PHOX phospholipid binding domain; SNX, SORTIN NEXIN; TGN/EE, Trans Golgi Network/Early Endosomes; Ub, Ubiquitin; VPS, VACUOLAR PROTEIN SORTING.
Figure 6.
Figure 6.
Exocytosis of Recycled Proteins, the Final Step. (A) Apical PM domains can receive exocytic material coming from the recycling pathway. RABE1 and RABA2A specifically regulate this pathway. RABE1 is attached to the membrane at the TGN/EE where the SCD complex (SCD1-SCD2) acts as a GEF exchanging GDP for GTP, which activates the GTPase. The SCD complex can also interact with SEC15B, a subunit of the EXOCYST complex. EXO15B specifically binds EXO70A1 at the apical PM. EXO70A1 is anchored to the membrane by interaction with PtdIns(4)P. The EXOCYST acts as a multi-subunit tethering complex bringing together R-SNAREs (VAMP721, VAMP722) and Qa-SNAREs (SYP121, SYP122) to form the fusion complex. Once the quadruple SNARE helix is formed, the factors SNAP33 and SEC11 regulate the fusion and complex disassembly. (B) Lateral recycling and exocytosis require the polar localization and action of the EXOCYST subunit EXO84B. (C) Basal secretion is specifically regulated by EXO70A1 that is anchored to PtdIns(4)P-enriched regions at the basal membrane. EXO70A1 interacts with Patelin3 (PATL3) that is related to regulation of exocytosis of recycling material and is also anchored to PtdIns(4)P. PALT3 function remains unknown.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Ahmed S.M., Nishida-Fukuda H., Li Y., McDonald W.H., Gradinaru C.C., Macara I.G. (2018). Exocyst dynamics during vesicle tethering and fusion. Nat. Commun. 9: 5140. - PMC - PubMed
    1. Ambrose C., Ruan Y., Gardiner J., Tamblyn L.M., Catching A., Kirik V., Marc J., Overall R., Wasteneys G.O. (2013). CLASP interacts with sorting nexin 1 to link microtubules and auxin transport via PIN2 recycling in Arabidopsis thaliana. Dev. Cell 24: 649–659. - PubMed
    1. Assaad F.F., Qiu J.-L., Youngs H., Ehrhardt D., Zimmerli L., Kalde M., Wanner G., Peck S.C., Edwards H., Ramonell K., Somerville C.R., Thordal-Christensen H. (2004). The PEN1 syntaxin defines a novel cellular compartment upon fungal attack and is required for the timely assembly of papillae. Mol. Biol. Cell 15: 5118–5129. - PMC - PubMed
    1. Avin-Wittenberg T., Bajdzienko K., Wittenberg G., Alseekh S., Tohge T., Bock R., Giavalisco P., Fernie A.R. (2015). Global analysis of the role of autophagy in cellular metabolism and energy homeostasis in Arabidopsis seedlings under carbon starvation. Plant Cell 27: 306–322. - PMC - PubMed
    1. Avin-Wittenberg T., et al. (2018). Autophagy-related approaches for improving nutrient use efficiency and crop yield protection. J. Exp. Bot. 69: 1335–1353. - PubMed

Publication types

LinkOut - more resources