Membrane Protein Targeting to the MVB/Lysosome

Davies, Brian A.; Lee, Jacqueline R. E.; Oestreich, Andrea J.; Katzmann, David J.

doi:10.1021/cr800473s

Cited by 50 publications

(41 citation statements)

References 165 publications

(545 reference statements)

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“…MVBs are most often described as fusing with lytic vacuoles in which proteins internalized from the plasma membrane are degraded (Davies et al, 2009). Linking MVBs to penetration resistance and to the introduction of components such as ROR2 and callose (see below) into the papilla suggests that a fusion event occurs between MVBs and the plasma membrane.…”

Section: Discussionmentioning

confidence: 99%

The Multivesicular Body-Localized GTPase ARFA1b/1c Is Important for Callose Deposition and ROR2 Syntaxin-Dependent Preinvasive Basal Defense in Barley

et al. 2010

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Host cell vesicle traffic is essential for the interplay between plants and microbes. ADP-ribosylation factor (ARF) GTPases are required for vesicle budding, and we studied the role of these enzymes to identify important vesicle transport pathways in the plant-powdery mildew interaction. A combination of transient-induced gene silencing and transient expression of inactive forms of ARF GTPases provided evidence that barley (Hordeum vulgare) ARFA1b/1c function is important for preinvasive penetration resistance against powdery mildew, manifested by formation of a cell wall apposition, named a papilla. Mutant studies indicated that the plasma membrane-localized REQUIRED FOR MLO-SPECIFIED RESISTANCE2 (ROR2) syntaxin, also important for penetration resistance, and ARFA1b/1c function in the same vesicle transport pathway. This was substantiated by a requirement of ARFA1b/1c for ROR2 accumulation in the papilla. ARFA1b/1c is localized to multivesicular bodies, providing a functional link between ROR2 and these organelles in penetration resistance. During Blumeria graminis f sp hordei penetration attempts, ARFA1b/1c-positive multivesicular bodies assemble near the penetration site hours prior to the earliest detection of callose in papillae. Moreover, we showed that ARFA1b/1c is required for callose deposition in papillae and that the papilla structure is established independently of ARFA1b/1c. This raises the possibility that callose is loaded into papillae via multivesicular bodies, rather than being synthesized directly into this cell wall apposition.

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Section: Discussionmentioning

confidence: 99%

The Multivesicular Body-Localized GTPase ARFA1b/1c Is Important for Callose Deposition and ROR2 Syntaxin-Dependent Preinvasive Basal Defense in Barley

et al. 2010

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“…Furthermore, we demonstrate that KCa3.1 is routed to lysosomes via the MVB pathway and that the main components of the ESCRT family of proteins are critical in this process. We investigated the roles of Tsg101 (ESCRT-I), CHMP4 (ESCRT-III), and VPS4, which are considered critical proteins for early, intermediate, and late steps of MVB sorting pathway, respectively (17,48). Previous studies revealed that TSG101 is required for the proper formation of MVBs (47,49), and that it is also important in selecting which proteins enter the MVB lumen and are delivered to the lysosomes, and which remain on the limiting membrane and escape degradation.…”

Section: Discussionmentioning

confidence: 99%

“…Initially, we focused on TSG101, a core component of the ESCRT-I complex (17,48). We coexpressed KCa3.1 with either WT, full-length TSG101 (TSG-F), or its NH 2 -terminally truncated form (TSG-3=).…”

Section: Kca31 Is Targeted To Mvb Via the Escrt Pathway-role Of Tsg101mentioning

confidence: 99%

“…ESCRT-II appears to function downstream or in parallel to ESCRT-I and facilitates the recruitment and assembly of ESCRT-III (composed of charged multivesicular body proteins, e.g., CHMP4). Finally, Vps4, a AAA ATPase, dissociates the ESCRT complex and facilitates the fusion of MVBs with lysosomes, resulting in the degradation of the cargo (17,48). However, recent studies have revealed that ESCRT-independent routes to lysosomes exist.…”

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confidence: 99%

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ESCRT-dependent targeting of plasma membrane localized KCa3.1 to the lysosomes

Balut

Gao

Murray

et al. 2010

American Journal of Physiology-Cell Physiology

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The number of intermediate-conductance, Ca2+-activated K+ channels (KCa3.1) present at the plasma membrane is deterministic in any physiological response. However, the mechanisms by which KCa3.1 channels are removed from the plasma membrane and targeted for degradation are poorly understood. Recently, we demonstrated that KCa3.1 is rapidly internalized from the plasma membrane, having a short half-life in both human embryonic kidney cells (HEK293) and human microvascular endothelial cells (HMEC-1). In this study, we investigate the molecular mechanisms controlling the degradation of KCa3.1 heterologously expressed in HEK and HMEC-1 cells. Using immunofluorescence and electron microscopy, as well as quantitative biochemical analysis, we demonstrate that membrane KCa3.1 is targeted to the lysosomes for degradation. Furthermore, we demonstrate that either overexpressing a dominant negative Rab7 or short interfering RNA-mediated knockdown of Rab7 results in a significant inhibition of channel degradation rate. Coimmunoprecipitation confirmed a close association between Rab7 and KCa3.1. On the basis of these findings, we assessed the role of the ESCRT machinery in the degradation of heterologously expressed KCa3.1, including TSG101 [endosomal sorting complex required for transport (ESCRT)-I] and CHMP4 (ESCRT-III) as well as VPS4, a protein involved in the disassembly of the ESCRT machinery. We demonstrate that TSG101 is closely associated with KCa3.1 via coimmunoprecipitation and that a dominant negative TSG101 inhibits KCa3.1 degradation. In addition, both dominant negative CHMP4 and VPS4 significantly decrease the rate of membrane KCa3.1 degradation, compared with wild-type controls. These results are the first to demonstrate that plasma membrane-associated KCa3.1 is targeted for lysosomal degradation via a Rab7 and ESCRT-dependent pathway.

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“…Ubiquitination at one (mono-ubiquitination) or multiple lysines (multiubiquitination) of a target protein regulates its endocytosis and sorting to the lysosomes for degradation (37). Given that Ub contains seven lysine residues, once a molecule of Ub is attached to the target protein, additional Ub molecules can be linked to Ub resulting in the formation of polyubiquitin chains.…”

mentioning

confidence: 99%