Evolutionary and Functional Diversity of Coronin Proteins

Xavier CP, Eichinger L, Fernandez MP, et al.

Publication Details

This chapter discusses various aspects of coronin phylogeny, structure and function that are of specific interest. Two subfamilies of ancient coronins of unicellular pathogens such as Entamoeba, Trypanosoma, Leishmania and Acanthamoeba as well as of Plasmodium, Babesia, and Trichomonas are presented in the first two sections. Their coronins generally bind to F-actin and apparently are involved in proliferation, locomotion and phagocytosis. However, there are so far no studies addressing a putative role of coronin in the virulence of these pathogens. The following section delineates genetic anomalies like the chimeric coronin-fusion products with pleckstrin homology and gelsolin domains that are found in amoeba. Moreover, most nonvertebrate metazoa appear to encode CRN8, CRN9 and CRN7 representatives (for these coronin symbols see Chapter 2) , but in e.g., Drosophila melanogaster and Caenorhabditis elegans a CRN9 is missing. The forth section deals with the evolutionary expansion of vertebrate coronins. Experimental data on the F-actin binding CRN2 of Xenopus (Xcoronin) including a Cdc42/Rac interactive binding (CRIB) motif that is also present in other members of the coronin protein family are discussed. Xenopus laevis represents a case for the expansion of the seven vertebrate coronins due to tetraploidization events. Other examples for a change in the number of coronin paralogs are zebrafish and birds, but (coronin) gene duplication events also occurred in unicellular protozoa. The fifth section of this chapter briefly summarizes three different cellular processes in which CRN4/CORO1A is involved, namely actin-binding, superoxide generation and Ca2+-signaling and refers to the largely unexplored mammalian coronins CRN5/CORO2A and CRN6/CORO2B, the latter binding to vinculin. The final section discusses how, by unveiling the aspects of coronin function in organisms reported so far, one can trace a remarkable evolution and diversity in their individual roles anticipating a rather complex and intricate involvement of coronins in a variety of cellular processes.


In the present book a sincere attempt has been made to provide a comprehensive overview on the coronin family of proteins. Other chapters of the book focus on phylogeny, structure, localization and, more interestingly, the roles of coronins in F-actin dynamics through interaction with actin and actin-binding proteins, in vesicular trafficking, in cancer, in certain pathogen virulence and on new possibilities for exploring coronin as an effective drug target. This chapter deals with members of the coronin protein family and specific aspects of coronin function that are not covered in the other chapters.

Currently two synonymous names are mainly used for the different members of the coronin protein family. One is based on a simple numbering system for mammalian coronins 1-7, while the other employs a number-letter system to specify coronins 1A ( = 1), 1B ( = 2), 1C ( = 3), 2A ( = 4) and 2B ( = 5).1-3 The current official nomenclature for vertebrate coronins from the HGNC (Human Gene Nomenclature Committee) delineates CORO1A, CORO1B, CORO1C, CORO2A, CORO2B, CORO6 and CORO7 symbols. The process to establish a new and unified nomenclature, which could be based on the one described in Chapter 4 by Reginald O. Morgan and M. Pilar Fernandez, is still in its infancy. Most likely this well-done proposal of a new nomenclature delineating twelve coronin subfamilies (CRN1-CRN12) based on their phylogenetic relationship will be modified by the researchers in the coronin field to preserve some historical aspects. Nevertheless, this chapter will already make use of the symbols of this proposed nomenclature, as the coronin proteins mainly discussed in this chapter, CRN10 and CRN12, are members of the five coronin subfamilies (CRN8, 9, 10, 11, 12) that are unnamed to date. Members of the CRN8 (e.g., Drosophila and Caenorhabditis short coronins) as well as of the CRN11 family (e.g., the single Saccharomyces coronin) are referred to in detail in Chapters 7 (Maria C. Shina and Angelika A. Noegel) and 6 (Meghal Gandhi and Bruce L. Goode), respectively. So far no experimental data for a CRN9 family member are available.

In this chapter, we first summarize the published data of coronin proteins from unicellular pathogens: CRN12, the phylogenetically oldest coronin and CRN10, the ancient coronin of alveolata and parabasalids. The Dictyostelium short coronin, the first published coronin (see Chapter 3 by Eugenio L. de Hostos), also belongs to the CRN12 family, but is discussed in Chapter 7. In the second part we put forward data on genetic anomalies of non vertebrate coronins, discuss the evolutionary expansion of selected coronins in vertebrates and present some of the data of vertebrate coronins that are not covered in the other chapters. Table 1 provides examples for each of the twelve coronin subfamilies and also includes some basic data on molecular properties, localization and function.

Table 1. Selected representatives of the coronin subfamilies.

Table 1

Selected representatives of the coronin subfamilies.

CRN12, the Phylogenetically Oldest Coronin

Members of the CRN12 family are present in Heterolobosea, Euglenozoa and Amoeba. Among these there are a number of human pathogens, like Entamoeba, Trypanosoma, Leishmania and Acanthamoeba. In macrophages survival of Mycobacteria is mediated by CRN4/ CORO1A-dependent activation of calcineurin (see Chapter 10 and Jayachandran et al4). This raises the question as to whether coronin might contribute to the pathogenicity of human pathogens.

Acanthamoeba is a medically significant pathogen causing the opportunistic disease granulomatous amoebic encephalitis and the amoebic keratitis of the eye. A. healyi Ahcoronin has a predicted molecular mass of 50 kDa and shows significant homology to D. discoideum CRN12. An N-terminal EGFP fusion protein of Ahcoronin is localized to the cytosol and the cell periphery with enrichment at the leading edge. Additionally, Ahcoronin transiently localizes to phagocytic cups, however, no enrichment was seen at the mature phagosome.5 This behaviour resembles the distribution of mammalian CRN4/CORO1A during phagosome maturation (see below) and is an interesting feature to trace the conservation of function. The C-terminus of Ahcoronin (aa 294-454) localized to the cell periphery with an enrichment at the leading edge similar to the full length protein. The EGFP-N terminus (aa 1-49) did not show any specific localization. Similarly, the WD-propeller and the conserved region (aa 50-293) showed a dispersed distribution indicating that the conserved region alone is not involved in actin binding. So far no correlation between pathogenicity and coronin expression in Acanthamoeba has been demonstrated. However, since coronin is localized in dynamic areas of the cell, the authors propose that this may indicate the involvement of Ahcoronin in dynamic processes that do require actin-dependent locomotion and phagocytosis.5

Leishmania is a protozoan that causes Leishmaniasis. A 56 kDa coronin protein was reported in Leishmania donovani that is also a member of the CRN12 subfamily. In immunolabelling studies, N-terminally GFP-tagged Leishmania coronin localized to filament-like actin structures in the cell periphery and uniformly throughout the cytoplasm, but was absent in the flagella. Additionally, the authors reported that ectopical co-expression of Leishmania actin and GFP-coronin in mammalian cells induced the formation of filamentous and patch-like structures.6 Leishmania actin and coronin specifically interacted with each other but the interaction was not strong enough to resist the treatment with non-ionic detergents. The leucine zipper motif in Leishmania coronin contains five heptads, which suggests the existence of coronin multimers in vivo (see also Chapter 5). Currently, no link between coronin expression and Leishmania pathogenicity has been established. However, similar to Acanthamoeba, studies investigating a potential role of coronin in the virulence of this pathogen will be interesting and may even open new possibilities for exploiting coronin as drug target.

CRN10, the Ancient Coronin of Alveolata and Parabasalids

Plasmodium falciparum, the major causative agent of human malaria, invades its intermediate host hepatocytes and erythrocytes. The driving force underlying parasite motility and host cell invasion has been suggested to be based on the parasite's actin cytoskeleton.7-9 P. falciparum coronin, a member of the CRN10 family has a calculated mass of 52 kDa and an apparent molecular weight of 42 kDa. It displays 35% identity with D. discoideum CRN12 and 27-32% identity with bovine and human coronin. A hallmark for most of the coronins is a leucine zipper motif at the C-terminus which is responsible for di- or multimerization. Surprisingly, this motif apparently is absent in P. falciparum CRN10. Cellular fractionation showed P. falciparum coronin in the cytosolic and Triton X-100 insoluble fraction. The authors suggest that a better understanding of coronin's role in actin dynamics as well as the identification of additional interacting proteins may help to define molecules critically involved in parasite survival.10 In this respect it is interesting that CRN10 from Babesiae bovis, bigemina, divergens and canis cosedimented with actin and was expressed at highest levels during the merozoite stage of this parasite in red blood cells.11

Trichomonas vaginalis, the causative agent of the most common nonviral sexually transmitted disease in human known as trichomoniasis, infects 250 to 350 million people worldwide. Trichomoniasis results in serious discomfort to women and is associated with adverse pregnancy outcome, preterm delivery, low-birth-weight infants and fertility, cervical cancer and increase in the transmission of HIV.12

A monoclonal antibody raised against a cytoskeletal fraction of T. vaginalis identified a closely spaced double-band in SDS-PAGE. The corresponding proteins had an apparent molecular weight of approximately 50 kDa, showed high sequence identity to D. discoideum CRN12 and were named Cor1 and Cor2. According to the proposed nomenclature they seem to represent the two CRN10 family members CRN10a and CRN10b that originated by relatively recent lineage-specific gene duplication in T. vaginalis (see Chapter 4). The T. vaginalis proteins display relatively weak percentage of identity (from 23-33%) with coronins from other organisms. However, this is expected considering the large evolutionary distance between the species.13 Immunolabelling and electron microscopic studies localized coronin to phagocytic cups and pseudopods of T. vaginalis amoeboid cells.14 Although the whole chain of events leading to host cell lysis remains to be fully elucidated, the authors speculate that coronin might play a major downstream role in a signalling pathway that leads to re-organization of the actin cytoskeleton and the adoption of the amoeboid form of the parasite.15 The generation of a coronin specific knockout in T. vaginalis16 will be crucial for investigation of this hypothesis. In addition the knock-out cells could be used to study the role of coronin in phagocytosis, pseudopod formation, cell motility and cell proliferation. The knock-out cells should also clarify whether coronin contributes to T. vaginalis virulence.

Genetic Anomalies in Nonvertebrate Coronin Proteins

Amoebae such as Dictyostelium discoideum, Dictyostelium purpureum and Entamoeba histolytica express a unique coronin-villin gene fusion product “villidin” with a presumed dual capacity to influence actin dynamics. The villidin homologs in D. discoideum (XP_636652) and D. purpureum (scaffold_52) exhibit approx. 82% amino acid identity to each other and approx. 33% amino acid identity with E. histolytica putative “villidin” (XP_655366). However, HMM (Hidden Markov Model) analysis revealed no authentic coronin domains in the latter and alignment with the Dictyostelium villidin was limited to the C-terminal region. Instead, a distinct actin-binding protein (ABPH, 1602 aa, gb:AF118397) was validated as the true villidin homolog from E. histolytica. It contains the coronin DUF1899, two WD40 domains and DUF1900 in its N-terminal region (for the DUF-domains and their contribution to the β-propeller scaffold please refer to Chapter 4) and in addition 3 pleckstrin homology (PH) domains and 3 gelsolin domains in its C-terminal region, similar to its Dictyostelium homolog (Fig. 1).

Figure 1. Schematic domain structures are shown for homologous villidin proteins from D.

Figure 1

Schematic domain structures are shown for homologous villidin proteins from D. discoideum (XP_636652, 1704 aa) and E. histolytica (“ABPH”, AF118397, 1602 aa). Both contain typical coronin domains at their amino termini in addition to 3 (more...)

Another interesting anomaly was detected by comparing matched species pairs for the invertebrate CRN8 and CRN9 subfamilies. Most (multicellular) invertebrate species have one representative in each subfamily in addition to a CRN7 representative. Additional searching of substantially complete genomes confirmed some overlooked pairs such as CRN9 (XP_969741) from Tribolium castaneum (red flour beetle), however, CRN9 orthologs could not be identified in genomic assembly data for D. melanogaster nor C. elegans. This indicates some selective gene loss or silencing subsequent to the original gene duplication event in early metazoa. Considering the evolutionary distance between CRN8 and CRN9 members, which share approx. 50% amino acid identity, it is plausible that they retain only limited functional redundancy. Thus the selective CRN9 loss in Drosophila and Caenorhabditis may be accompanied by measurable phenotypic change when compared to other insect and nematode models.

Evolutionary Expansion of Selected Coronins in Vertebrates

A X. laevis homolog of Dictyostelium coronin—Xcoronin—has been described as a protein of 480 amino acids with a molecular mass of 57 kDa and 67% identity to human CRN4/CORO1A. Two apparent isoforms were reported for this X. laevis coronin, Xcoronin A and B, with 93% identity to each other, capable of forming homo- and hetero-oligomers.17,18 A recent database analysis identified seven coronins in X. laevis and Xenopus tropicalis, which are orthologs of the human coronins CRN1-7 with identities between 55 to 84% (see Chapter 4). From these analyses it turned out that Xcoronin A and B both belong to the CRN2 family and, moreover, that CRN2a and CRN2b probably result from a recent whole genome duplication in X. laevis (but not X. tropicalis) about 40 Mya ago.19 CRN2a (Xcoronin A) and CRN2b (Xcoronin B) show 94% identity to the single X. tropicalis CRN2 copy (BC064872; CORO1C). Thus, X. tropicalis (western clawed frog) has seven coronins, i.e., CRN1-CRN7, whereas X. laevis (African clawed frog) has at least nine coronins, including duplicates of CRN2/CORO1C and CRN6/CORO2B. Due to the genome duplication X. laevis would have been expected to have 14 coronins, i.e., CRN1a-CRN7a and CRN1b and CRN7b, but the missing duplicates may have suffered genetic mishaps during the genome duplication event or may have been silenced (i.e.,eroded by mutation) for toxicity or lack of need, as seems to have occurred in teleost fishes like zebrafish (Table 2), that underwent a unique tetraploidization event over 300 million years ago, subsequent to their divergence from jawless and cartilagenous fish. Note that the X. laevis CRN2a and CRN2b copies are different from variant isoforms of the same gene, as described for the human CRN2. For human CRN2 (CORO1C) three variants have been detected at the mRNA and protein level (NM_014325, AM849477, AM849478),20 derived from three transcripts from the same gene by differential splicing. In general, amphibia (e.g., X. tropicalis) and reptiles (e.g., the lizard Anolis carolinensis) seem to have the full complement of seven vertebrate coronins, whereas birds (e.g., chicken and zebrafinch) possess most coronin loci dispersed in their genomes with the exception of CRN4/ CORO1A which has not yet been detected (Table 2). Other organisms that underwent whole genome duplication from a diploid to a tetraploid state include all teleost fishes like medaka and zebrafish, but selective gene duplication and/or extensive gene loss obscure such ancient events in unicellular protozoa like Cryptosporidium, Trichomonas, Entamoeba and Saccharomyces. The zebrafish genome, for example, has duplicate copies of CRN5/CORO2A, CRN6/CORO2B and CRN2/CORO1C on distinct chromosomes; other coronin duplicates appear to have been lost or silenced (Table 2).

Table 2. Coronin repertoires and anomalies in selected vertebrate genomes.

Table 2

Coronin repertoires and anomalies in selected vertebrate genomes.

The N- and C- terminal domains of Xcoronin (A and B), CRN2a and CRN2b, were shown to be critical for optimal binding to F-actin.17 Xcoronin forms a stable dimer via its C-terminal leucine zipper motif. Dimerization of Xcoronin was found to be crucial for its proper colocalization with F-actin at the cell periphery and plays an important role in Rac induced lamellipoidial extensions and cell spreading.17 However, X. laevis CRN2 did not significantly associate with F-actin stress fibres and was absent from focal adhesions and cell-cell contacts unlike CRN5/CORO2A.21 The inability of the dimerization mutants to localize to the cell periphery emphasizes the significance of dimerization for optimal binding to actin filaments as was shown for CRN2/ CORO1C.22 Interestingly, a short sequence stretch that resembles the Cdc42/Rac interactive binding (CRIB) motif was found between amino acids 119 and 134 of X. laevis CRN2 and could act as a potential binding site for the activated GTP-binding proteins Rac and Cdc42 involved in the regulation of the actin cytoskeleton.17,18 Cdc42/Rac effectors contain the conserved CRIB motif that binds the effector domain of Cdc42/Rac GTPases in a GTP-dependent manner.23,24 Based on the reported CRIB motif in Xenopus CRN2 we searched for similar motifs in human coronins and found that this sequence stretch is highly conserved in human CRN4/CORO1A, CRN1/CORO1B, CRN2/CORO1C and CRN3/CORO6, less conserved in human CRN5/ CORO2A, CRN6/CORO2B and Dictyostelium CRN12 and not conserved in human CRN7/ CORO7 (Fig. 2A). In support of a functional role, the CRIB motif is located in a loop which is surface accessible and stretches from β-sheet D of blade 2 with most of the amino acids in the loop region, ending with β-sheet A of blade 3 (Fig. 2B). In Swiss 3T3 cells it has been shown that active Rac induced lamellipodial extension and redistribution of CRN2/CORO1C.22 Further experiments should unravel the roles of different coronins in Rac- and Cdc42-mediated signalling to the actin cytoskeleton (Xavier CP, unpublished).

Figure 2. A) Putative CRIB motif in coronins.

Figure 2

A) Putative CRIB motif in coronins. Sequence alignment of a putative CRIB motif of different Homo sapiens coronins (Hs-CRN1-7) and D. discoideum coronin (Dd-CRN12) with X. laevis coronins (Xl-CRN2a, 2b). Sequence of β-propeller blade 2 (yellow (more...)

Tissue Specific Expression and Putative Functions of Mammalian Coronins Not Covered in the Other Chapters

The seven mammalian coronins exhibit a distinct pattern of expression across cell types and tissues.1 The best-characterized CRN4/CORO1A is virtually exclusively expressed in thymocytes, T-cells, macrophages and neutrophils.25-30 It has been shown to function in actin-dependent processes as well as in specific functions unrelated to actin. For a detailed view on mammalian CORO1A regarding its interaction with actin please refer to Chapters 5 and 6 and to Chapter 11, 5th section, for details regarding actin-unrelated functions please refer to Chapter 10 and also Chapter 11, 5th section.

In order to provide an outline of some of the interesting aspects of mammalian CRN4/ CORO1A, three apparently unrelated roles are considered. Firstly, CORO1A has been shown to interact with and regulate F-actin and has been detected in dynamic regions of the submembranous actin cytoskeleton of leucocytes with important implications in the immune system.27,28,31 A soluble pool of CORO1A in human phagocytic leukocytes forms high-molecular-weight complexes that are solubilized by PI3-kinase activity and may be involved in forming the F-actin structures in early phagosome formation.32 In addition, ActA-positive Listeria monocytogenes have been found to recruit CORO1A to their F-actin tails in infected host cells.33 Secondly, a putative function reported for CORO1A in the immune system points to the regulation of superoxide generation in connection with a phagocytic vacuole.30 CORO1A binds C-terminally to p40phox, a cytosolic subunit of the NADPH oxidase complex involved in the generation of the microbicidal superoxide burst in neutrophils. Finally, upon internalization of pathogens like Mycobacteria, Salmonella and Heliobacter as well as of latex beads by macrophages, CORO1A is transiently recruited to the site of entry.34-38 Whether or not pathogen-derived molecules like lipoamide dehydrogenase C (LpdC) or a cholesterol-specific receptor molecule are involved in this process is currently discussed.39-41 In contradiction to earlier studies, CORO1A was found dispensable for the phagocytic process itself.4 Interestingly, the retention of CORO1A on the phagosome inhibits its later fusion with lysosomes and prevents the phagocytosed pathogens from degradation. Here, mechanisms regulating CORO1A transcription,42 dissociation of CORO1A from the phagosome accompanied by phosphorylation on serine residues involving PKC43 and calcineurin-signaling4 may be involved.

A recent study delineated CRN4/CORO1A as an important factor for the development of the autoimmune disease systemic lupus erythematosus (SLE). A spontaneous nonsense mutation of coronin-1A (c.784C>T; p.Gln262X) leading to a truncated and non-functional protein suppressed the development of the autoimmune disease in lupus-prone mice.44 The mutation led to phenotypes involving the actin cytoskeleton as well as calcium signaling. In this respect the quite different phenotypes observed for the CORO1A knockout mouse strains independently generated by Föger et al27 and Jayachandran et al4 are combined in this additional mouse model. Mutated CORO1A resulted in a reduced number of single positive CD4+ and CD8+ T cells, including the naïve and activated subsets, increased rate of apoptosis, decreased proliferation rates, increased levels of cellular F-actin, impaired migration in response to chemokines, and reduced initial calcium entry upon activation.44 As a consequence of a reduced T helper activity levels of polyclonal serum IgG and anti-dsDNA antibodies were also decreased. Thus, the coronin-1A mutation effectively suppressed cellular as well as humoral manifestations of SLE.44 These recent data once more emphasize an important role of coronin proteins in, but certainly not limited to, the immune system (see also Chapter 10) as well as development, regeneration and cancer progression (see Chapter 11).

CRN1/CORO1B is ubiquitously expressed at high levels in most of the tissues in contrast to CRN2/CORO1C, which is ubiquitously expressed but at low levels. Three splice variants of CRN3/CORO6 are expressed in the brain (NP_624354, NP_624355, NP_624356). CORO7/ CRN7 is ubiquitously expressed but at lower levels compared to other mammalian coronins. Specific functions of CORO1B, CORO1C and CORO7 are described in their respective chapters (5, 6, 9, 11).

Mammalian CRN5/CORO2A (IR10, ClipinB), a 525 amino acid containing protein, was isolated by screening a human epidermal cDNA library. Northern blot analysis demonstrated high expression levels in brain in addition to lower expression in epidermis, colon, prostate, testis and lung. Studies regarding intracellular localization, F-actin binding and its possible role in F-actin dynamics are yet to be established.45

Mammalian CRN6/CORO2B (Clipin C) is one of the predominantly expressed coronin proteins in the nervous system. It is enriched in the brain and expressed at lower levels in other tissues. It consists of 475 aa with a predicted molecular mass of 54 kDa and shows 44% amino acid identity with CORO1A and 61% with CORO2A. Immunocytochemical analysis revealed colocalization of CORO2B with F-actin at focal adhesions, neurite tips and stress fibers. In addition a considerable amount was reported to be dispersed in the cell body. Immunoprecipitation studies showed an association of CORO2B with vinculin, a major component of focal contacts supporting its localization at focal adhesions. In mouse brain CORO2B localized in cerebral cortex, hippocampus, thalamus, olfactory bulb and cerebellum. In the cerebellum the Purkinje cell layer was intensely labeled. Through cosedimentation assays a clear association of CORO2B with F-actin was demonstrated. Altogether the authors propose CORO2B as a possible candidate that would act as a cytoskeleton-membrane connector, implicated in the control of cell adhesions and cell movements in neuronal cells.21

Outlook: The Remarkable Functional Diversity of Coronin Proteins

The actin cytoskeleton is one of the most fascinating cellular networks that mediates a variety of essential biological processes critical for the survival of the cell.46 Its dynamic properties provide the basic force for various processes like cell migration, endocytosis, vesicular trafficking and cytokinesis.47-49 In order to efficiently execute all these dynamic processes the differential regulation and recruitment of a plethora of actin-binding proteins with distinctive activities is required. One of the major actin binding proteins that has been extensively studied in recent years is coronin.

Coronin was first identified in the social amoeba D. discoideum (see Chapter 3). Identification of coronin in other unicellular organisms and higher organisms followed.1-3 A number of aspects contribute to a rather complex situation for the function of coronin proteins. Firstly, except for F-actin no other binding partner of the WD-domain of coronins has been confirmed yet, even though for other WD-proteins as well as the structurally related Kelch-proteins various interaction partners have been identified (see Chapters 1 and 2). As the WD-propeller domain is regarded as a platform for protein-protein interactions, various binding partners can be anticipated and may disclose a new variety of distinct functions of coronins. Secondly, the C-terminal coiled coil domain of coronins obviously is involved in oligomerization and Arp2/3 binding. Associated with a change in the three-dimensional shape of the coronin molecule are the proper subcellular localization, but also its activity or binding specificity are likely regulated (see Chapter 6). Thirdly, phosphorylation of specific residues in several coronin proteins have been shown to regulate localisation, oligomerization and interaction with other proteins. Possibly, other posttranslational modifications still await detection.

Starting with a single coronin gene in a simple, yet complex eukaryote, the family of coronin proteins expanded to seven paralogues in vertebrates. Gene duplications in some vertebrates might have resulted in up to fourteen different coronin proteins that all might have acquired different cellular functions. In addition, splice variants of mammalian coronins have been detected, that further amplify the functional diversity. By unravelling the cellular functions of coronins in a wide range of organisms, from amoeba to the highly evolved mammals, one can trace a remarkable evolutionary and functional diversity. It is clear that we are only beginning to understand the functional roles of the diverse coronins and we anticipate the involvement of coronins in other cellular processes yet to be explored.


We thank Andreas Hofmann for kindly preparing the structural homology models included in Figure 2B (see also Chapter 5). CSC is supported by the DFG (NO 113/13-3) and Köln Fortune. Futhermore, grant supposrts by the Imhoff-and Maria-Pesch-Foundations awarded to CSC are gratefully acknowledged.


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