Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs

Traub, Linton M.; Lukacs, Gergely L.

doi:10.1242/jcs.03385

Cited by 87 publications

(86 citation statements)

References 167 publications

(216 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, the application of AMPA, but not NMDA, can induce the ubiquitination of AMPA receptors [40][41][42] , which can be recruited to clathrin-coated pits for endocytosis via the APs epsin and eps15 (ref. 43). Therefore, further studies are warranted to clarify whether and how TARPs are involved in the various forms of AMPA receptor trafficking.…”

Section: Discussionmentioning

confidence: 99%

Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

et al. 2013

View full text Add to dashboard Cite

Long-term depression (LTD) underlies learning and memory in various brain regions. Although postsynaptic AMPA receptor trafficking mediates LTD, its underlying molecular mechanisms remain largely unclear. Here we show that stargazin, a transmembrane AMPA receptor regulatory protein, forms a ternary complex with adaptor proteins AP-2 and AP-3A in hippocampal neurons, depending on its phosphorylation state. Inhibiting the stargazin-AP-2 interaction disrupts NMDA-induced AMPA receptor endocytosis, and inhibiting that of stargazin-AP-3A abrogates the late endosomal/lysosomal trafficking of AMPA receptors, thereby upregulating receptor recycling to the cell surface. Similarly, stargazin's interaction with AP-2 or AP-3A is necessary for low-frequency stimulus-evoked LTD in CA1 hippocampal neurons. Thus, stargazin has a crucial role in NMDA-dependent LTD by regulating two trafficking pathways of AMPA receptors-transport from the cell surface to early endosomes and from early endosomes to late endosomes/lysosomes-through its sequential binding to AP-2 and AP-3A.

show abstract

Section: Discussionmentioning

confidence: 99%

Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

et al. 2013

View full text Add to dashboard Cite

show abstract

“…One possible mechanism that might augment the ubiquitin signal is iron-induced oligomerization of the transporter. This could occur initially at the plasma membrane where the transporter first encounters iron and would serve to consolidate a cohort of ubiquitylated Fet3-Ftr1 at the plasma membrane to facilitate endocytosis and in endosomes to increase the efficiency of Rsp5-mediated ubiquitylation and/or the avidity with which the Vps27-Hse1 MVBsorting receptor captures the cargo (Piper and Luzio, 2007;Traub and Lukacs, 2007). An alternative possibility is that iron shock induces association of Fet3-Ftr1 with another protein that confers MVB sorting (and possibly endocytosis).…”

Section: Discussionmentioning

confidence: 99%

Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome

Strochlic

Schmiedekamp

Lee

et al. 2008

MBoC

View full text Add to dashboard Cite

Endocytosed proteins are either delivered to the lysosome to be degraded or are exported from the endosomal system and delivered to other organelles. Sorting of the Saccharomyces cerevisiae reductive iron transporter, composed of the Fet3 and Ftr1 proteins, in the endosomal system is regulated by available iron; in iron-starved cells, Fet3-Ftr1 is sorted by Snx3/Grd19 and retromer into a recycling pathway that delivers it back to the plasma membrane, but when starved cells are exposed to iron, Fet3-Ftr1 is targeted to the lysosome-like vacuole and is degraded. We report that iron-induced endocytosis of Fet3-Ftr1 is independent of Fet3-Ftr1 ubiquitylation, and after endocytosis, degradation of Fet3-Ftr1 is mediated by the multivesicular body (MVB) sorting pathway. In mutant cells lacking any component of the ESCRT protein-dependent MVB sorting machinery, the Rsp5 ubiquitin ligase, or in wild-type cells expressing Fet3-Ftr1 lacking cytosolic lysyl ubiquitin acceptor sites, Fet3-Ftr1 is constitutively sorted into the recycling pathway independent of iron status. In the presence and absence of iron, Fet3-Ftr1 transits an endosomal compartment where a subunit of the MVB sorting receptor (Vps27), Snx3/Grd19, and retromer proteins colocalize. We propose that this endosome is where Rsp5 ubiquitylates Fet3-Ftr1 and where the recycling and degradative pathways diverge. INTRODUCTIONThe endocytic pathway is initiated with the internalization of protein and lipid cargo from the plasma membrane. After endocytosis, internalized molecules transit through the endosomal system, a network of interconnected organelles that process and sort cargo molecules back to the plasma membrane, to other organelles, or to lysosomes for degradation. In mammalian cells, early endosomes are pleiomorphic organelles composed of vacuolar domains that contain lumenal vesicles and tubular domains that lead into and emanate from the vacuolar portion. This distinct architecture has functional significance. The tubular elements of the organelle are regions where the majority of internalized plasma membrane proteins and lipids are exported and recycled from the endosomal system via bulk flow and cargo-specific processes (Mayor et al., 1993;Maxfield and McGraw, 2004;Bonifacino and Rojas, 2006). Cargo proteins that are not exported are delivered to lysosomes and many of these are degraded. This occurs via an active, signal-mediated event in which these proteins are targeted to the vacuolar region of the endosome where they are incorporated into vesicles that bud from the limiting membrane into the lumen of the organelle (Piper and Katzmann, 2007). During endosome maturation lumenal vesicles accrue until fusion of the late endosome with the lysosome results in degradation of these vesicles and their contents. A central sorting function of the endosomal system is thus to segregate cargo to be exported from the endosome from cargo to be degraded via lysosomal proteolysis.The core components of the recycling (retrograde) and degradative sorting pathways have be...

show abstract

“…DUBs may affect this step by direct deubiquitylation of receptors or through influencing components of the vesicular entry routes. The ubiquitin-dependent interaction of cargo molecules with clathrin-coated vesicle (CCV) adaptor proteins, such as epsin, promotes endocytosis (257). The Drosophila DUB Fat Facets (Faf) (USP9X in humans) interacts directly with the epsin homolog Liquid facets (Laf).…”

Section: Influence On Cell Physiology Through Control Of Receptmentioning

confidence: 99%

Deubiquitylases From Genes to Organism

Clague

Barsukov

Coulson

et al. 2013

Physiological Reviews

368

384

View full text Add to dashboard Cite

Ubiquitylation is a major posttranslational modification that controls most complex aspects of cell physiology. It is reversed through the action of a large family of deubiquitylating enzymes (DUBs) that are emerging as attractive therapeutic targets for a number of disease conditions. Here, we provide a comprehensive analysis of the complement of human DUBs, indicating structural motifs, typical cellular copy numbers, and tissue expression profiles. We discuss the means by which specificity is achieved and how DUB activity may be regulated. Generically DUB catalytic activity may be used to 1) maintain free ubiquitin levels, 2) rescue proteins from ubiquitin-mediated degradation, and 3) control the dynamics of ubiquitin-mediated signaling events. Functional roles of individual DUBs from each of five subfamilies in specific cellular processes are highlighted with an emphasis on those linked to pathological conditions where the association is supported by whole organism models. We then specifically consider the role of DUBs associated with protein degradative machineries and the influence of specific DUBs upon expression of receptors and channels at the plasma membrane.

show abstract

Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs

Cited by 87 publications

References 167 publications

Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

Stargazin regulates AMPA receptor trafficking through adaptor protein complexes during long-term depression

Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome

Deubiquitylases From Genes to Organism

Contact Info

Product

Resources

About