The NECAP PHear domain increases clathrin accessory protein binding potential

Ritter, Brigitte; Denisov, A. Yu.; Philie, Jacynthe; Allaire, Patrick D.; Legendre-Guillemin, Valerie; Zylbergold, Peter; Gehring, Kalle; McPherson, Peter S.

doi:10.1038/sj.emboj.7601836

Cited by 29 publications

(45 citation statements)

References 68 publications

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“…The NECAP proteins show a high degree of sequence similarity and share a common structural organization, including two peptide motifs for interaction with the clathrin adapter proteins AP-1 and AP-2 (Ritter et al, 2007(Ritter et al, , 2003. We have recently shown that NECAP1 cooperates with AP-2 to ensure efficient vesicle formation for clathrin-mediated endocytosis ; in contrast, the data presented here demonstrate a central role for NECAP2 in AP-1-mediated fast recycling from early endosomes.…”

Section: Discussioncontrasting

confidence: 53%

“…The two members of the family, NECAP1 and NECAP2, share a high degree of sequence and structural similarity. At their N-terminus, the NECAPs encode a pleckstrin homology (PH)-like domain that functions as a protein-binding module (Ritter et al, 2007). In addition, NECAPs display peptide motifs at their C-terminus that promote interactions with the clathrin adaptor complexes AP-1 and AP-2 .…”

Section: Introductionmentioning

confidence: 99%

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NECAP2 controls clathrin coat recruitment to early endosomes for fast endocytic recycling

Chamberland

Antonow

Santos

et al. 2016

Journal of Cell Science

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Endocytic recycling returns receptors to the plasma membrane following internalization and is essential to maintain receptor levels on the cell surface, re-sensitize cells to extracellular ligands and for continued nutrient uptake. Yet, the protein machineries and mechanisms that drive endocytic recycling remain ill-defined. Here, we establish that NECAP2 regulates the endocytic recycling of EGFR and transferrin receptor. Our analysis of the recycling dynamics revealed that NECAP2 functions in the fast recycling pathway that directly returns cargo from early endosomes to the cell surface. In contrast, NECAP2 does not regulate the clathrin-mediated endocytosis of these cargos, the degradation of EGFR or the recycling of transferrin along the slow, Rab11-dependent recycling pathway. We show that protein knockdown of NECAP2 leads to enlarged early endosomes and causes the loss of the clathrin adapter AP-1 from the organelle. Through structure-function analysis, we define the protein-binding interfaces in NECAP2 that are crucial for AP-1 recruitment to early endosomes. Together, our data identify NECAP2 as a pathway-specific regulator of clathrin coat formation on early endosomes for fast endocytic recycling.

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Section: Discussioncontrasting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

NECAP2 controls clathrin coat recruitment to early endosomes for fast endocytic recycling

Chamberland

Antonow

Santos

et al. 2016

Journal of Cell Science

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“…Recently, it has been reported that the N-terminal region of NECAP also interacts with FXDXF motifs with a similar affinity to the ␣-adaptin appendage (50). The structure of this domain revealed that it belongs to the pleckstrin homology domain superfamily, but the lipid-binding residues are not conserved.…”

Section: Discussionmentioning

confidence: 99%

Solitary and Repetitive Binding Motifs for the AP2 Complex α-Appendage in Amphiphysin and Other Accessory Proteins

Olesen

Ford

Schmid

et al. 2008

Journal of Biological Chemistry

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Adaptor protein (AP) complexes bind to transmembrane proteins destined for internalization and to membrane lipids, so linking cargo to the accessory internalization machinery.This machinery interacts with the appendage domains of APs, which have platform and ␤-sandwich subdomains, forming the binding surfaces for interacting proteins. Proteins that interact with the subdomains do so via short motifs, usually found in regions of low structural complexity of the interacting proteins. So far, up to four motifs have been identified that bind to and partially compete for at least two sites on each of the appendage domains of the AP2 complex. Motifs in individual accessory proteins, their sequential arrangement into motif domains, and partial competition for binding sites on the appendage domains coordinate the formation of endocytic complexes in a temporal and spatial manner. In this work, we examine the dominant interaction sequence in amphiphysin, a synapse-enriched accessory protein, which generates membrane curvature and recruits the scission protein dynamin to the necks of coated pits, for the platform subdomain of the ␣-appendage. The motif domain of amphiphysin1 contains one copy of each of a DX(F/W) and FXDXF motif. We find that the FXDXF motif is the main determinant for the high affinity interaction with the ␣-adaptin appendage. We describe the optimal sequence of the FXDXF motif using thermodynamic and structural data and show how sequence variation controls the affinities of these motifs for the ␣-appendage.Clathrin-mediated endocytosis is the process whereby proteins and lipids destined for internalization from the plasma membrane are packaged into vesicles with the aid of a clathrin coat. Purified coated vesicles from brain contain three major components as follows: clathrin, AP180, and AP2 complexes (1-3). Clathrin triskelia oligomerize to provide the scaffold around the forming vesicle (and can form similar cages in solution (4)). With its terminal domain, clathrin interacts with other endocytic proteins, including the AP2 7 complex, AP180, epsin, disabled-2 (Dab2), and amphiphysin. These interactions are mediated via short motifs; for example, clathrin binds to amphiphysin through motifs such as LLDLD or PWXXW (5, 6). Because oligomeric clathrin presents an array of binding sites for these motifs, it serves as a network hub, organizing binding partners within the lattice. The AP complexes, as well as many accessory proteins and alternative cargo adaptors such as AP180, Dab2, epsin, and amphiphysin, recruit clathrin to PtdIns(4,5)P 2 -rich areas in the membrane and promote its polymerization into a lattice. Because of its significant number of interaction partners, another key hub in the endocytic interactome is the AP2 complex (7-9). It consists of four subunits (␣, ␤2, 2, and 2) and forms a stable heterotetramer in solution (10). Using electron microscopy it was shown that the AP2 complex can be subdivided into the following: (i) a trunk domain, which interacts with cargo proteins and PtdIns(4,5)P 2...

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“…These proteins function in trafficking at various subcellular locations. AAK1 and NECAP1 and -2 interact with AP-2 and are involved in the formation of cargo-laden CCVs at the plasma membrane during endocytosis (43,45). Interestingly, like clavesins, FENS1, CVAK104, and enthoprotin/epsinR are localized to membranes of the TGN and/or endosomes and are involved in trafficking at these compartments (23, 46 -50).…”

Section: Discussionmentioning

confidence: 99%

The Clavesin Family, Neuron-specific Lipid- and Clathrin-binding Sec14 Proteins Regulating Lysosomal Morphology

Katoh

Ritter

Gaffry

et al. 2009

Journal of Biological Chemistry

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Clathrin-coated vesicles (CCVs) originating from the transGolgi network (TGN) provide a major transport pathway from the secretory system to endosomes/lysosomes. Herein we describe paralogous Sec14 domain-bearing proteins, clavesin 1/CRALBPL and clavesin 2, identified through a proteomic analysis of CCVs. Clavesins are enriched on CCVs and form a complex with clathrin heavy chain (CHC) and adaptor protein-1, major coat components of TGN-derived CCVs. The proteins co-localize with markers of endosomes and the TGN as well as with CHC and adaptor protein-1. A membrane mimic assay using the Sec14 domain of clavesin 1 reveals phosphatidylinositol 3,5-bisphosphate as a specific lipid partner. Phosphatidylinositol 3,5-bisphosphate is localized to late endosomes/lysosomes, and interestingly, isoform-specific knockdown of clavesins in neurons using lentiviral delivery of interfering RNA leads to enlargement of a lysosome-associated membrane protein 1-positive membrane compartment with no obvious influence on the CCV machinery at the TGN. Since clavesins are expressed exclusively in neurons, this new protein family appears to provide a unique neuron-specific regulation of late endosome/lysosome morphology.

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The NECAP PHear domain increases clathrin accessory protein binding potential

Cited by 29 publications

References 68 publications

NECAP2 controls clathrin coat recruitment to early endosomes for fast endocytic recycling

NECAP2 controls clathrin coat recruitment to early endosomes for fast endocytic recycling

Solitary and Repetitive Binding Motifs for the AP2 Complex α-Appendage in Amphiphysin and Other Accessory Proteins

The Clavesin Family, Neuron-specific Lipid- and Clathrin-binding Sec14 Proteins Regulating Lysosomal Morphology

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