Epsin: Inducing membrane curvature

Horvath, Caroline A.J.; Broeck, Davy Vanden; Boulet, Gaëlle; Bogers, Johannes; Wolf, M.

doi:10.1016/j.biocel.2006.12.004

Cited by 69 publications

(65 citation statements)

References 21 publications

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“…From a mechanistic perspective, the NaV1.7 trafficking pathway identified here greatly extends the findings of Laedermann et al, who reported that the Nedd4-2 ubiquitin ligase monoubiquitinates NaV1.7 to signal the channel's endocytosis (6). Our results suggest that induction of membrane curvature by Eps15 (26,27) to trigger clathrin-mediated endocytosis is required for CRMP2-mediated endocytosis of NaV1.7 via the formation of a CRMP2/Numb/Eps15/ Nedd4-2 complex. If CRMP2 is not SUMOylated, these interactions are strengthened, culminating in accumulation of the channel into early and recycling endosomes.…”

Section: Discussionsupporting

confidence: 86%

“…One possibility may be differential recruitment of the endocytic machinery or CRMP2 itself. Nedd4 proteins regulate trafficking of multiple sodium channels (6, 37) whereas Numb and Eps15 proteins are general players in clathrin-mediated endocytosis (18,19,27), so specificity is unlikely endowed by these proteins. Likely, the specificity is conferred by CRMP2, as its expression and modifications causally influence NaV1.7.…”

Section: Discussionmentioning

confidence: 99%

“…As NaV1.7 endocytosis requires monoubiquitination by the ubiquitin ligase Nedd4-2 (24) and Numb-a CRMP2 protein partner acts as a scaffold between Nedd4 (25) and the endocytic machinery (19)-we hypothesized that recruitment of these proteins by CRMP2 may promote NaV1.7 internalization. Additionally, Numb can recruit Eps15 (19,26,27). Together, these proteins compose the machinery required to mark a protein for endocytosis (28) and initiate clathrin-mediated endocytosis by enabling interactions between Eps15 and a monoubiquitinated cargo.…”

Section: Significancementioning

confidence: 99%

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Hierarchical CRMP2 posttranslational modifications control NaV1.7 function

Dustrude

Moutal

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

112

255

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Voltage-gated sodium channels are crucial determinants of neuronal excitability and signaling. Trafficking of the voltage-gated sodium channel NaV1.7 is dysregulated in neuropathic pain. We identify a trafficking program for NaV1.7 driven by hierarchical interactions with posttranslationally modified versions of the binding partner collapsin response mediator protein 2 (CRMP2). The binding described between CRMP2 and NaV1.7 was enhanced by conjugation of CRMP2 with small ubiquitin-like modifier (SUMO) and further controlled by the phosphorylation status of CRMP2. We determined that CRMP2 SUMOylation is enhanced by prior phosphorylation by cyclin-dependent kinase 5 and antagonized by Fyn phosphorylation. As a consequence of CRMP2 loss of SUMOylation and binding to NaV1.7, the channel displays decreased membrane localization and current density, and reduces neuronal excitability. Preventing CRMP2 SUMOylation with a SUMO-impaired CRMP2-K374A mutant triggered NaV1.7 internalization in a clathrindependent manner involving the E3 ubiquitin ligase Nedd4-2 (neural precursor cell expressed developmentally down-regulated protein 4) and endocytosis adaptor proteins Numb and epidermal growth factor receptor pathway substrate 15. Collectively, our work shows that diverse modifications of CRMP2 cross-talk to control NaV1.7 activity and illustrate a general principle for regulation of NaV1.7.NaV1.7 sodium channel | trafficking | CRMP2 | SUMOylation | phosphorylation

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

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Hierarchical CRMP2 posttranslational modifications control NaV1.7 function

Dustrude

Moutal

Yang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

112

255

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“…Even if the identity between tick and yeast ATG genes is limited (for example, HlATG4 shares 25% identity with yeast ATG4), amino acid residues that are essential for the function of yeast Atg proteins are highly conserved in HlATG proteins (Umemiya-Shirafuji R, et al unpublished curved membranes, as has been reported for the formation of curved membranes of primary endocytic vesicles. 31 By screening EP insertion lines, Chen et al 32 identified a line mutated for pax. Paxillin belongs to the actin-binding proteins, which associate with the cytoplasmic domain of integrins, and in this way regulates cell migration, proliferation and survival.…”

Section: The Genetics Of Autophagy In Arthropodsmentioning

confidence: 99%

Autophagy and its physiological relevance in arthropods: Current knowledge and perspectives

Malagoli¹,

Abdalla²,

Cao³

et al. 2010

Autophagy

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“…As the α0 helices of ENTH domains are inserted into membranes for anchoring (34), both epsinR and Ent3p orient their N termini toward the membrane. However, due to the opposite binding orientation of Habc domains, the ENTH-bound yeast Vti1p and mammalian vti1b will be placed oppositely (Fig.…”

Section: Discussionmentioning

confidence: 99%

Epsin N-terminal homology domains bind on opposite sides of two SNAREs

Wang

Gossing

Fang

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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SNARE proteins are crucial for membrane fusion in vesicular transport. To ensure efficient and accurate fusion, SNAREs need to be sorted into different budding vesicles. This process is usually regulated by specific recognition between SNAREs and their adaptor proteins. How different pairs of SNAREs and adaptors achieve their recognition is unclear. Here, we report the recognition between yeast SNARE Vti1p and its adaptor Ent3p derived from three crystal structures. Surprisingly, this yeast pair Vti1p/Ent3p interacts through a distinct binding site compared to their homologues vti1b/epsinR in mammals. An opposite surface on Vti1p_Habc domain binds to a conserved area on the epsin N-terminal homology (ENTH) domain of Ent3p. Two-hybrid, in vitro pull-down and in vivo experiments indicate this binding interface is important for correct localization of Vti1p in the cell. This previously undescribed discovery that a cargo and adaptor pair uses different binding sites across species suggests the diversity of SNARE-adaptor recognition in vesicular transport.cargo recogniton | Vti1p sorting | crystallography S ecretion and intracellular transport rely on vesicular traffic in eukaryotic cells. Vesicle transport can be divided into multiple steps: budding, targeting, tethering, and fusion (1). During the fusion process, the vesicles fuse with the target membrane and release the cargo proteins. The key players in membrane fusion are SNAREs (soluble N-ethylmaleimide-sensitive factor attachment receptor) (2, 3). SNARE proteins are defined by their characteristic heptad repeat SNARE domains. During the fusion process, four SNARE domains (usually one on the vesicle membrane and three on the target membrane) associate to form a stable twisted four-helix bundle, bringing the two opposing membranes in close contact and facilitating fusion (3). Thus, SNAREs are regarded as the basic element in membrane fusion (2-4).Vesicle fusions are specific processes that require the specific localization of SNAREs on different membranes. There are 24 SNAREs in yeast and about 40 SNAREs in mammals with specific subcellular localization (5-7) (Fig. S1). SNAREs are recruited as cargo proteins to different subcellular membranes by adaptor proteins (8). The maintenance of compartment identity requires highly specific recognition between SNAREs and their adaptor proteins during vesicle budding. Distinct from many cargo proteins, most SNAREs do not contain the short, linear sorting motifs that are recognized by common adaptors like AP or GGA for sorting into vesicles (there are few exceptions including Vamp4, which contains the signal motif dileucine recognized by AP) (9-11). It has been reported, however, that the N-terminal three-helix bundle (Habc domain) of many SNAREs is recognized through interaction with the ENTH (epsin N-terminal homology) domain of a few epsin-like family proteins (8,12,13).The epsin-like family is characterized by a conserved N-terminal ENTH domain (11,14,15) and consists of four epsin proteins (epsin1, epsin2, epsin3, epsi...

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Epsin: Inducing membrane curvature

Cited by 69 publications

References 21 publications

Hierarchical CRMP2 posttranslational modifications control NaV1.7 function

Hierarchical CRMP2 posttranslational modifications control NaV1.7 function

Autophagy and its physiological relevance in arthropods: Current knowledge and perspectives

Epsin N-terminal homology domains bind on opposite sides of two SNAREs

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