Generation of high curvature membranes mediated by direct endophilin bilayer interactions

Farsad, Khashayar; Ringstad, Niels; Takei, Kohji; Floyd, Scott R.; Rose, Kristin; Camilli, Pietro De

doi:10.1083/jcb.200107075

Cited by 552 publications

(616 citation statements)

References 17 publications

Supporting

Mentioning

581

Contrasting

Unclassified

Order By: Relevance

“…Bif-1, also known as SH3GLB1 or Endophilin B1, was originally discovered as a Bax-binding protein 16,17 . Although Bif-1 has liposome tubulation activity in vitro, it appears as though this protein does not localize to transferrinpositive endosomes 18 . Recent studies have shown that Bif-1 associates with membranes of intracellular organelles, such as the Golgi apparatus 18, 19 and mitochondria 20, 21 , and has been implicated in vesicle formation and membrane dynamics.…”

mentioning

confidence: 95%

Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis

et al. 2007

View full text Add to dashboard Cite

Autophagy is an evolutionally conserved "self-eating" process. Although the genes essential for autophagy (termed Atg) have been identified in yeast, the molecular mechanism of how these Atg proteins control autophagosome formation in mammalian cells remains to be elucidated. Here, we demonstrate that Bif-1 (also known as Endophilin B1) interacts with Beclin 1 through UVRAG and acts as a positive mediator of the class III PI3-kinase (PI3KC3). In response to nutrition deprivation, Bif-1 localizes to autophagosomes where it colocalizes with Atg5, as well as LC3. Furthermore, loss of Bif-1 suppresses autophagosome formation. While the SH3 domain of Bif-1 is sufficient for binding to UVRAG, both the BAR and SH3 domains are required for Bif-1 to activate PI3KC3 and induce autophagosome formation. We also found that Bif-1 ablation prolongs cell survival under nutrient starvation. Moreover, knockout of Bif-1 significantly enhances the development of spontaneous tumors in mice. These findings suggest that Bif-1 joins the UVRAG-Beclin 1 complex as a potential activator of autophagy and tumor suppressor.Autophagy is a tightly orchestrated intracellular process for bulk degradation of cytoplasmic proteins or organelles that appears to be essential for many physiological processes such as cellular homeostasis, development, differentiation, tissue remodeling, cell survival and death, innate immunity, and pathogenesis in various organisms 1-4 . The process of autophagic degradation is initiated when a portion of the cytosolic components are sequestered in cupshaped membrane structures called isolation membranes 1, 2, 5, 6 . The isolation membranes are elongated and eventually sealed to become double-membrane vesicles called autophagosomes, which are then fused with lysosomes resulting in degradation of the enclosed components. Eighteen autophagy-related (Atg) genes have been characterized in S. cerevisiae and can be categorized into four functional groups: (1) the Atg1 protein kinase complex regulating the induction of autophagy, (2) the class III PI3-kinase (PI3KC3) lipid kinase complex controlling vesicle nucleation, (3) the Atg12-Atg5 and Atg8-phosphatidylethanolamine conjugation pathways for vesicle expansion and completion, and (4) the Atg protein retrieval system 2, 7 . Beclin 1, the mammalian homologue of yeast Atg6, is a key component of the PI3KC3 complex, which plays an essential role in autophagosome formation 8-11 . Although the phosphatidylinositol 3-phosphate (PtdIns-3-P) generated by PI3KC3 has been proposed to control membrane dynamics during autophagosome formation 3 , the molecular mechanism underlying this process remains unknown. Results Loss of Bif-1 suppresses caspase-independent cell deathWe have previously reported that Bif-1 localizes to mitochondria and regulates the activation of Bax and Bak during apoptosis induced by intrinsic death stimuli 21 . To examine Bif-1 localization in mouse embryonic fibroblast (MEF) cells during serum deprivation, we added a pancaspase inhibitor, z-VAD-fmk, to ...

show abstract

mentioning

confidence: 95%

Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis

et al. 2007

View full text Add to dashboard Cite

show abstract

“…These proteins, which interact with dynamin through its C-terminal pro/arg-rich domain (PRD), fall into several functionally distinct classes. They include actin-binding proteins, e.g., cortactin and mAbp1 Kessels et al, 2001); scaffolding molecules, e.g., intersectin, syndapin, grb2, and nck, which link dynamin to N-WASP and other proteins (Gout et al, 1993;Roos and Kelly, 1998;Peter et al, 2004;Schmitz et al, 2004); and membrane-active molecules, e.g., endophilin and amphiphysin, that can sense and/or generate membrane curvature (Schmidt et al, 1999;Farsad et al, 2001;Peter et al, 2004). In the case of actin dynamics, there is growing evidence that dynamin can regulate the activity of some of these accessory proteins (Schafer et al, 2002).…”

mentioning

confidence: 99%

SNX9 Regulates Dynamin Assembly and Is Required for Efficient Clathrin-mediated Endocytosis

Soulet

Yarar

Leonard

et al. 2005

MBoC

188

233

View full text Add to dashboard Cite

Dynamin, a central player in clathrin-mediated endocytosis, interacts with several functionally diverse SH3 domaincontaining proteins. However, the role of these interactions with regard to dynamin function is poorly defined. We have investigated a recently identified protein partner of dynamin, SNX9, sorting nexin 9. SNX9 binds directly to both dynamin-1 and dynamin-2. Moreover by stimulating dynamin assembly, SNX9 stimulates dynamin's basal GTPase activity and potentiates assembly-stimulated GTPase activity on liposomes. In fixed cells, we observe that SNX9 partially localizes to clathrin-coated pits. Using total internal reflection fluorescence microscopy in living cells, we detect a transient burst of EGFP-SNX9 recruitment to clathrin-coated pits that occurs during the late stages of vesicle formation and coincides spatially and temporally with a burst of dynamin-mRFP fluorescence. Transferrin internalization is inhibited in HeLa cells after siRNA-mediated knockdown of SNX9. Thus, our results establish that SNX9 is required for efficient clathrin-mediated endocytosis and suggest that it functions to regulate dynamin activity. INTRODUCTIONThe GTPase dynamin plays a critical role in clathrin-mediated endocytosis (CME; Hinshaw, 2000). Dynamin self-assembles into a collar-like structure around the necks of deeply invaginated clathrin-coated pits (CCPs) where it is believed to directly mediate membrane fission and vesicle release. Dynamin is also associated with newly formed coated pits (Damke et al., 1994;Evergren et al., 2004) where it may function to regulate early stages of coated pit maturation (Sever et al., 2000a;Song and Schmid, 2003;Song et al., 2004).Although only one isoform of dynamin exists in Drosophila and in Caenorhabditis elegans, mammals express at least three isoforms, which are ϳ70% identical to each other. Dynamin-1, the first identified protein in the dynamin family, is expressed exclusively in neuronal cells where it functions in synaptic vesicle recycling (Shpetner and Vallee, 1989;Nakata et al., 1991;Sontag et al., 1994). Dynamin-2 is ubiquitously expressed (Cook et al., 1994;Sontag et al., 1994) and localizes to endocytic CCPs where it functions, like dynamin-1, in endocytosis (Damke et al., 1994;Altschuler et al., 1998). However, dynamin-2 may also be involved in vesicle formation at the Golgi Kreitzer et al., 2000), in regulating actin dynamics (Schafer, 2004), in cell signaling (Kranenburg et al., 1999;Fish et al., 2000), and has recently been localized to the centriole (Thompson et al., 2004). Dynamin-3, which is most highly expressed in testis but also detectable in neurons (Gray et al., 2003) and in lung (Nakata et al., 1993), has been less well studied.Dynamins are atypical GTPases, distinguished by their large size, low affinity for GTP, and high intrinsic rates of GTP hydrolysis (Sever et al., 2000b;Song and Schmid, 2003). Moreover, dynamin can self-assemble in solution (Hinshaw and Schmid, 1995) or on liposome templates into rings and spiral-like structures (Stowell et al., 199...

show abstract

“…In vivo, over-expression of the BAR domain of human Amphiphysin II in tissue culture cells causes invagination of the plasma membrane to form internal tubules that resemble the T-tubules of skeletal muscle involved in excitationcontraction coupling (6). As well as the BAR domain, the N-terminal region also plays an important role in membrane bending (7). This auxilliary region is likely to undergo a random coil to helical transition on engagement with the membrane (2).…”

mentioning

confidence: 99%

The Crystal Structure of the BAR Domain from Human Bin1/Amphiphysin II and Its Implications for Molecular Recognition

et al. 2006

View full text Add to dashboard Cite

BaR domains are found in proteins that bind and remodel membranes and participate in cytoskeletal and nuclear processes. Here, we report the crystal structure of the BAR domain from the human Bin1 protein at 2.0 Å resolution. Both the quaternary and tertiary architectures of the homodimeric Bin1 BAR domain are built upon "knobs-into-holes" packing of side chains, like those found in conventional left-handed coiled-coils, and this packing governs the curvature of a putative membrane-engaging concave face. Our calculations indicate that the Bin1 BAR domain contains two potential sites for protein-protein interactions on the convex face of the dimer. Comparative analysis of structural features reveals that at least three architectural subtypes of the BAR domain are encoded in the human genome, represented by the Arfaptin, Bin1/ Amphiphysin, and IRSp53 BAR domains. We discuss how these principal groups may differ in their potential to form regulatory heterotypic interactions.

show abstract

Generation of high curvature membranes mediated by direct endophilin bilayer interactions

Cited by 552 publications

References 17 publications

Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis

Bif-1 interacts with Beclin 1 through UVRAG and regulates autophagy and tumorigenesis

SNX9 Regulates Dynamin Assembly and Is Required for Efficient Clathrin-mediated Endocytosis

The Crystal Structure of the BAR Domain from Human Bin1/Amphiphysin II and Its Implications for Molecular Recognition

Contact Info

Product

Resources

About