Centre for the Molecular Genetics of Development publications

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A redox mechanism controls differential DNA binding activities of hypoxia-inducible factor (HIF) 1a and the HIF-like factor
(Amer Soc Biochemistry Molecular Biology Inc, 2000) Lando, D.; Pongratz, I.; Poellinger, L.; Whitelaw, M.; Centre for the Molecular Genetics of Development
Hypoxia-inducible factor 1α (HIF-1α) and the HIF-like factor (HLF) are two highly related basic Helix-Loop-Helix/Per-Arnt-Sim (bHLH/PAS) homology transcription factors that undergo dramatically increased function at low oxygen levels. Despite strong similarities in their activation mechanisms (e.g. they both undergo rapid hypoxia-induced protein stabilization, bind identical target DNA sequences, and induce synthetic reporter genes to similar degrees), they are both essential for embryo survival via distinct functions during vascularization (HIF-1α) or catecholamine production (HLF). It is currently unknown how such specificity of action is achieved. We report here that DNA binding by HLF, but not by HIF-1α, is dependent upon reducing redox conditions. In vitro DNA binding and mammalian two-hybrid assays showed that a unique cysteine in the DNA-binding basic region of HLF is a target for the reducing activity of redox factor Ref-1. Although the N-terminal DNA-binding domain of HIF-1α can function in the absence of Ref-1, we found that the C-terminal region containing the transactivation domain requires Ref-1 for full activity. Our data reveal that the hypoxia-inducible factors are subject to complex redox control mechanisms that can target discrete regions of the proteins and are the first to establish a discriminating control mechanism for differential regulation of HIF-1α and HLF activity.
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Precision genetic modification of the mammalian genome
(Bureau of Rural Sciences, 2000) Rathjen, Peter David; Verma, P. J.; Centre for the Molecular Genetics of Development; School of Molecular and Biomedical Science
The potential of transgenesis to achieve rational and efficient animal improvement has been recognised for some time. Commercial application of this technology has been restricted by inherent limitations of existing methodologies, and a shortage of candidate genes for transfer. Recent advances, notably in the areas of mammalian reproductive technologies and whole genome sequencing, provide, for the first time, realistic prospects for directed genetic modification of the mammalian genome in a commercially relevant manner. Augmentation of traditional breeding objectives with transgenic technologies can be expected to improve the efficiency of existing breeding programs, while the opportunity to introduce novel genes and gene combinations, and modify endogenous genes with precision, raises the possibility of developing animals with novel properties, specifically designed for niche markets of enormous value. Modification of the genome by transgenesis is therefore likely to become an important component of livestock industries. While Australia has access to the relevant technologies, the pace of international progress has not been matched locally, and this could compromise the competitiveness of local industries. Animal transgenesis provides an example of how strategic investment in key emergent technologies at a local level can be critical for both the establishment and maintenance of industries of international importance.
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Forkhead transcription factors, Fkh1p and Fkh2p, collaborate with Mcm1p to control transcription required for M-phase
(Elsevier Science, 2000) Sharma, Raman Kumar; Reynolds, David M.; Shevchenko, Andrej; Shevchenko, Anna; Goldstone, Sherilyn D.; Dalton, Stephen; Centre for the Molecular Genetics of Development; School of Molecular and Biomedical Science
Background: The ‘CLB2 cluster’ in Saccharomyces cerevisiae consists of approximately 33 genes whose transcription peaks in late G2/early M phase of the cell cycle. Many of these genes are required for execution of the mitotic program and then for cytokinesis. The transcription factor SFF (SWI5 factor) is thought to regulate a program of mitotic transcription in conjunction with the general transcription factor Mcm1p. The identity of SFF has yet to be determined; hence further understanding of the mechanisms that regulate entry to M phase at the transcriptional level requires characterization of SFF at the molecular level. Results: We have purified the biochemical activity corresponding to SFF and identified it as the forkhead transcription factor Fkh2p. Fkh2p assembles into ternary complexes with Mcm1p on both the SWI5 and CLB2 cell-cycle-regulated upstream activating sequence (UAS) elements in vitro, and in an Mcm1p-dependent manner in vivo. Another closely related forkhead protein, Fkh1p, is also recruited to the CLB2 promoter in vivo. We show that both FKH1 and FKH2 play essential roles in the activation of the CLB2 cluster genes during G2–M and in establishing their transcriptional periodicity. Hence, Fkh1p and Fkhp2 show the properties expected of SFF, both in vitro and in vivo. Conclusions: Forkhead transcription factors have redundant roles in the control of CLB2 cluster genes during the G2–M period of the cell cycle, in collaboration with Mcm1p.
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Co-localization of FAM and AF-6, the mammalian homologues of Drosophila faf and canoe, in mouse eye development
(Elsevier Science, 2000) Kanai-Azuma, Masami; Mattick, John S.; Kaibuchi, Kozo; Wood, Stephen Andrew; Centre for the Molecular Genetics of Development; School of Molecular and Biomedical Science
The Drosophila fat facets and canoe genes regulate non-neural cell fate decisions during ommatidium formation. We have shown previously that the FAM (fat facets in mouse) de-ubiquitinating enzyme regulates the function of AF-6, (mammalian canoe homologue), in the MDCK epithelial cell line (Taya et al., 1998. The Ras target AF-6 is a substrate of the fam deubiquitinating enzyme. J. Cell Biol. 142, 1053–1062). We report here that the expression of the FAM and AF-6 proteins overlaps extensively in the mouse eye from embryogenesis to maturity, especially in the non-neural epithelia including the retinal pigment epithelium, subcapsular epithelium of the lens and corneal epithelium. Expression is not limited to the epithelia however, as FAM and AF-6 also co-localize during lens fibre development as well as in sub-populations of the neural retina.
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The grapes checkpoint coordinates nuclear envelope breakdown and chromosome condensation
(Nature Publishing Group, 2000) Yu, K.; Saint, R.; Sullivan, W.; Centre for the Molecular Genetics of Development
Mutations in the embryonic Drosophila Grapes/Chk1 checkpoint result in an abbreviated interphase, chromosome condensation defects and metaphase delays. To clarify the relationship between these phenotypes, we simultaneously timed multiple nuclear and cytoplasmic events in mutant grp-derived embryos. These studies support a model in which grp disrupts an S-phase checkpoint, which results in progression into metaphase with incompletely replicated chromosomes. We also show that chromosome condensation is independent of the state of DNA replication in the early embryo. Therefore, grp condensation defects are not a direct consequence of entering metaphase with incompletely replicated chromosomes. Rather, initiation of chromosome condensation (ICC) occurs at the normal time in grp-derived embryos, but the shortened interval between ICC and metaphase does not provide sufficient time to complete condensation. Our results suggest that these condensation defects, rather than incomplete DNA replication, are responsible for the extensive metaphase delays observed in grp-derived embryos. This analysis provides an example of how the loss of a checkpoint can disrupt the timing of multiple events not directly monitored by that checkpoint. These results are likely to apply to vertebrate cells and suggest new strategies for destroying checkpoint-compromised cancer cells.
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Intracellular and extracellular leukemia inhibitory factor proteins have different cellular activities that are mediated by distinct protein motifs
(American Society for Cell Biology, 2000) Haines, Bryan Peter; Voyle, Roger Bruce; Rathjen, Peter David; Centre for the Molecular Genetics of Development; School of Molecular and Biomedical Science
Although many growth factors and cytokines have been shown to be localized within the cell and nucleus, the mechanism by which these molecules elicit a biological response is not well understood. The cytokine leukemia inhibitory factor (LIF) provides a tractable experimental system to investigate this problem, because translation of alternatively spliced transcripts results in the production of differentially localized LIF proteins, one secreted from the cell and acting via cell surface receptors and the other localized within the cell. We have used overexpression analysis to demonstrate that extracellular and intracellular LIF proteins can have distinct cellular activities. Intracellular LIF protein is localized to both nucleus and cytoplasm and when overexpressed induces apoptosis that is inhibited by CrmA but not Bcl-2 expression. Mutational analysis revealed that the intracellular activity was independent of receptor interaction and activation and reliant on a conserved leucine-rich motif that was not required for activation of cell surface receptors by extracellular protein. This provides the first report of alternate intracellular and extracellular cytokine activities that result from differential cellular localization of the protein and are mediated by spatially distinct motifs.
Open Access
New mutations in MID1 provide support for loss of function as the cause of X-linked Optiz syndrome
(Oxford Univ Press, 2000) Cox, T.; Allen, L.; Cox, L.; Hopwood, B.; Goodwin, B.; Haan, E.; Suthers, G.; Centre for the Molecular Genetics of Development
Opitz syndrome (OS) is a genetically heterogeneous malformation disorder. Patients with OS may present with a variable array of malformations that are indicative of a disturbance of the primary midline developmental field. Mutations in the C-terminal half of MID1, an RBCC (RING, B-box and coiled-coil) protein, have recently been shown to underlie the X-linked form of OS. Here we show that the MID1 gene spans at least 400 kb, almost twice the distance originally reported and has a minimum of six mRNA isoforms as a result of the alternative use of 5' untranslated exons. In addition, our detailed mutational analysis of MID1 in a cohort of 15 patients with OS has resulted in the identification of seven novel mutations, two of which disrupt the N-terminus of the protein. The most severe of these (E115X) is predicted to truncate the protein before the B-box motifs. In a separate patient, a missense change (L626P) was found that also represents the most C-terminal alteration reported to date. As noted with other C-terminal mutations, GFP fusion constructs demonstrated that the L626P mutant formed cytoplasmic clumps in contrast to the microtubular distribution seen with the wild-type sequence. Notably, however, both N-terminal mutants showed no evidence of cytoplasmic aggregation, inferring that this feature is not pathognomonic for X-linked OS. These new data and the finding of linkage to MID1 in the absence of a demonstrable open reading frame mutation in a further family support the conclusion that X-linked OS results from loss of function of MID1.
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Spinal motor axons and neural crest cells use different molecular guides for segmental migration through the rostral half-somite
(John Wiley & Sons Inc, 2000) Koblar, S.; Krull, C.; Pasquale, E.; McLennan, R.; Peale, F.; Cerretti, D.; Bothwell, M.; Centre for the Molecular Genetics of Development
The peripheral nervous system in vertebrates is composed of repeating metameric units of spinal nerves. During development, factors differentially expressed in a rostrocaudal pattern in the somites confine the movement of spinal motor axons and neural crest cells to the rostral half of the somitic sclerotome. The expression patterns of transmembrane ephrin-B ligands and interacting EphB receptors suggest that these proteins are likely candidates for coordinating the segmentation of spinal motor axons and neural crest cells. In vitro, ephrin-B1 has indeed been shown to repel axons extending from the rodent neural tube (Wang & Anderson, 1997). In avians, blocking interactions between EphB3 expressed by neural crest cells and ephrin-B1 localized to the caudal half of the somite in vivo resulted in loss of the rostrocaudal patterning of trunk neural crest migration (Krull et al., 1997). The role of ephrin-B1 in patterning spinal motor axon outgrowth in avian embryos was investigated. Ephrin-B1 protein was found to be expressed in the caudal half-sclerotome and in the dermomyotome at the appropriate time to interact with the EphB2 receptor expressed on spinal motor axons. Treatment of avian embryo explants with soluble ephrin-B1, however, did not perturb the segmental outgrowth of spinal motor axons through the rostral half-somite. In contrast, under the same treatment conditions with soluble ephrin-B1, neural crest cells migrated aberrantly through both rostral and caudal somite halves. These results indicate that the interaction between ephrin-B1 and EphB2 is not required for patterning spinal motor axon segmentation. Even though spinal motor axons traverse the same somitic pathway as neural crest cells, different molecular guidance mechanisms appear to influence their movement.
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The HMG Box Transcription Factor Gene Sox14 Marks a Novel Subset of Ventral Interneurons and Is Regulated by Sonic Hedgehog
(Academic Press, 2000) Hargrave, Murray; Karunaratne, Asanka; Cox, Liza; Wood, Stephen Andrew; Koopman, Peter; Yamada, Toshiya; Centre for the Molecular Genetics of Development; School of Molecular and Biomedical Science
Cell-type diversity along the dorsoventral axis of the developing neural tube is influenced by factors secreted by groups of cells at the dorsal and ventral midline. Upon reception of these signals, precursor cells express specific sets of transcription factors which, in turn, play critical roles in cell-type specification. Here we report the cloning and characterization of Sox14, a novel and highly conserved member of the Sry-related Sox transcription factor gene family, in mouse and chick. Sox14 expression is restricted to a limited population of neurons in the developing brain and spinal cord of both species. Sox14 marks a subset of interneurons at a defined dorsoventral position adjacent to ventral motor neurons in the spinal cord. In vivo grafting of chick notochord tissue to ectopic positions adjacent to the developing spinal cord altered the expression domain of Sox14. Furthermore, expression of Sox14 in spinal cord explants was found to be regulated by Sonic hedgehog in a dose-dependent manner. These data implicate a novel class of transcription factors in dorsoventral cell-type specification in the spinal cord.
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Pictures in cell biology. A functional marker for Drosophila chromosomes in vivo
(Elsevier Science London, 2000) Saint, R.; Clarkson, M.; Centre for the Molecular Genetics of Development
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Analysis of Meiosis in Fixed and Live Oocytes by Light Microscopy
(Cold Spring Harbor Laboratory Press, 2000) Matthies, H.; Clarkson, M.; Saint, R.; Namba, R.; Hawley, R.; Centre for the Molecular Genetics of Development
Open Access
Reversible programming of pluripotent cell differentiation
(Company of Biologists, 2000) Lake, J.; Rathjen, Joy R.; Remiszewski, Jacqueline Lee; Rathjen, Peter David; Centre for the Molecular Genetics of Development; School of Molecular and Biomedical Science
We have undertaken an in vitro differentiation analysis of two related, interconvertible, pluripotent cell populations, ES and early primitive ectoderm-like (EPL) cells, which are most similar in morphology, gene expression, cytokine responsiveness and differentiation potential in vivo to ICM and early primitive ectoderm, respectively. Pluripotent cells were differentiated in vitro as aggregates (embryoid bodies) and the appearance and abundance of cell lineages were assessed by morphology and gene expression. Differentiation in EPL cell embryoid bodies recapitulated normal developmental progression in vivo, but was advanced in comparison to ES cell embryoid bodies, with the rapid establishment of late primitive ectoderm specific gene expression, and subsequent loss of pluripotent cell markers. Nascent mesoderm was formed earlier and more extensively in EPL cell embryoid bodies, and resulted in the appearance of terminally differentiated mesodermal cell types prior to and at higher levels than in ES cell embryoid bodies. Nascent mesoderm in EPL cell embryoid bodies was not specified but could be programmed to alternative fates by the addition of exogenous factors. EPL cells remained competent to form primitive endoderm even though this is not the normal fate of primitive ectoderm in vivo. The establishment of primitive ectoderm-like gene expression and inability to participate in embryogenesis following blastocyst injection is therefore not directly associated with restriction in the ability to form extra-embryonic lineages. However, the EPL cell embryoid body environment did not support differentiation of primitive endoderm to visceral endoderm, indicating the lack of an inductive signal for visceral endoderm formation deduced to originate from the pluripotent cells. Similarly, the inability of EPL cells to form neurons when differentiated as embryoid bodies was attributable to perturbation of the differentiation environment and loss of inductive signals rather than a restricted differentiation potential. Reversion of EPL cells to ES cells was accompanied by restoration of ES cell-like differentiation potential. These results demonstrate the ability of pluripotent cells to adopt developmentally distinct, stable cell states with altered differentiation potentials.
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Regulated expression of alternate transcripts from the mouse oncostatin M gene: Implications for interleukin-6 family cytokines
(W B Saunders - Elsevier, 2000) Voyle, Roger Bruce; Rathjen, Peter David; Centre for the Molecular Genetics of Development; School of Molecular and Biomedical Science : Biochemistry
Oncostatin M (OSM) is a member of the IL-6 family of polyfunctional cytokines. The characterized murine OSM transcript consists of three exons and encodes a secreted protein. Investigations of mOSM expression using the ribonuclease protection assay demonstrated novel sites of expression in undifferentiated but not differentiated pluripotent cells, and revealed the existence of alternatively spliced mOSM transcripts. cDNAs representing a novel mOSM transcript (mOSM 13) containing exon 1 spliced directly to exon 3 were isolated from bone marrow using Rapid Amplification of cDNA Ends (RACE) PCR and RT-PCR approaches. Expression of the mOSM 13 transcript was regulated in a tissue-specific manner and independently of mOSM transcript production, suggesting that its production is biologically significant. Splicing of exon 1 directly to exon 3 disrupts the OSM open reading frame of mOSM 13. Initiation of translation at sites within exon 3 of mOSM 13 would yield N-terminally truncated OSM proteins that are localized within the cell. The omission of exon 2 by alternate splicing and the production of intracellular proteins with alternate biological activities are conserved among several IL-6 family cytokines and are one manifestation of a more general phenomenon; the production of alternate cytokine transcripts encoding intracellular and extracellular proteins.
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On the conservation of function of the Drosophila Fat facets deubiquitinating enzyme and Fam, its mouse homolog
(Springer Verlag, 2000) Chen, Xiaoguang; Overstreet, Erin; Wood, Stephen Andrew; Fischer, J. A.; Centre for the Molecular Genetics of Development; School of Molecular and Biomedical Science : Biochemistry
Fat facets is a Drosophila deubiquitinating enzyme required for eye development and early embryogenesis. Genetic evidence suggests that Fat facets deubiquitinates and thereby prevents the proteasomal degradation of specific substrates. The Drosophila Liquid facets protein is implicated as the critical substrate of Fat facets in the eye. A mouse homolog of Fat facets, called Fam, has been identified. The results of biochemical experiments implicate two different proteins, Af-6 and β-catenin, as substrates for Fam. Here, the functional relationship between Fat facets and Fam is explored. We show that Fam can substitute for Fat facets in all of its essential functions in Drosophila. In addition, we tested the hypothesis that Canoe and Armadillo, the Drosophila homologs of Af-6 and β-catenin, respectively, are important substrates for Fat facets in the Drosophila eye. We found no genetic evidence to support a role for either Canoe or Armadillo in the essential Fat facets pathways in Drosophila eye development. The significance of these results is discussed in light of the biochemical experiments that suggest that Af-6 and β-catenin are substrates of Fam.
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ARID proteins come in from the desert
(Elsevier Science London, 2000) Kortschak, R.; Tucker, P.; Saint, R.; Centre for the Molecular Genetics of Development
Members of the recently discovered ARID (AT-rich interaction domain) family of DNA-binding proteins are found in fungi and invertebrate and vertebrate metazoans. ARID-encoding genes are involved in a variety of biological processes including embryonic development, cell lineage gene regulation and cell cycle control. Although the specific roles of this domain and of ARID-containing proteins in transcriptional regulation are yet to be elucidated, they include both positive and negative transcriptional regulation and a likely involvement in the modification of chromatin structure.
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Motor axon pathfinding in the peripheral nervous system
(Pergamon-Elsevier Science Ltd, 2000) Krull, C.; Koblar, S.; Centre for the Molecular Genetics of Development
Functional motor performance is dependent upon the correct assemblage of neural circuitry, a process initiated during embryonic development. How is the complicated neural circuitry that underlies functional behavior formed? During early stages of development, motor neurons extend their axons in a precise manner to their target destinations where they form fine synaptic connections. This process is not random but rather, highly stereotyped and specific. Results of recent studies indicate that positive and negative molecules influence particular steps in the navigation of motor axons to their targets. These molecules include, but are not limited to, members of the Semaphorin family and their receptors, Neuropilins and Plexins, Slits and their Robo receptors, members of the Eph family, extracellular matrix molecules, Hepatocyte Growth Factor/Scatter Factor, peanut agglutinin-binding glycoproteins, and neural cell adhesion molecule. The developing avian peripheral nervous system has served as an excellent model system for many years for studies of the basic cellular interactions that underlie motor axon pathfinding. The principal advantage for the experimental use of the avian embryo is the ease of access to early developmental events. Fine microsurgical manipulations, difficult at best in mouse embryonic development, are readily accomplished in avian embryos and have provided a powerful approach to unraveling the cellular interactions that govern motor axon pathfinding. These approaches, combined in recent years with molecular biology, have begun to produce critical insights into the mechanisms that sculpt cellular architecture during neural development.
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Receptor tyrosine kinase signaling regulates different modes of Groucho-dependent control of Dorsal
(Dell Press, 2000) Hader, T.; Wainwright, D.; Shandala, T.; Saint, R.; Taubert, H.; Bronner, G.; Jackle, H.; Centre for the Molecular Genetics of Development
Transcriptional control of the Drosophila terminal gap gene huckebein (hkb) depends on Torso (Tor) receptor tyrosine kinase (RTK) signaling and the Rel/NFB homolog Dorsal (Dl) . Dl acts as an intrinsic transcriptional activator in the ventral region of the embryo, but under certain conditions, such as when it is associated with the non-DNA-binding co-repressor Groucho (Gro), it is converted into a repressor . Gro is recruited to the enhancer element in the vicinity of Dl by sequence-specific transcription factors such as Dead Ringer (Dri) . We examined the interplay between Dl, Gro and Dri on the hkb enhancer and show that when acting over a distance, Gro abolishes rather than converts Dl activator function. Reducing the distance between Dl- and Dri-binding sites, however, switches Dl into a Gro-dependent repressor that overrides activation of transcription. Both of the distance-dependent regulatory options of Gro - quenching and silencing of transcription- are inhibited by RTK signaling. These data describe a newly identified mode of function for Gro when acting in concert with Dl. RTK signaling provides a way of modulating Dl function by interfering either with Gro activity or with Dri-dependent recruitment of Gro to the enhancer.
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Expression of EphA4, Ephrin-A2 and Ephrin-A5 during axon outgrowth to the hindlimb indicates potential roles in pathfinding
(Karger, 2000) Eberhart, J.; Swartz, M.; Koblar, S.; Pasquale, E.; Tanaka, H.; Krull, C.; Centre for the Molecular Genetics of Development
During neural development, spinal motor axons extend in a precise manner from the ventral portion of the developing spinal cord to innervate muscle targets in the limb. Although classical studies in avians have characterized the cellular interactions that influence motor axon pathfinding to the limb, less is known about the molecular mechanisms that mediate this developmental event. Here, we examine the spatiotemporal distributions of the EphA4 receptor tyrosine kinase (RTK) and its cognate ligands, ephrin-A2 and ephrin-A5, on motor neurons, their axons and their pathways to the avian hindlimb to determine whether these molecules may influence axonal projections. The expression patterns of EphA4, ephrin-A2 and ephrin-A5 mRNAs and proteins are highly complex and appear to exhibit some overlap during motor axon outgrowth and pathfinding to the hindlimb, reminiscent of the co-expression of Eph RTKs and ephrins in the retinotectal system. EphA4, similar to the carbohydrate moiety polysialic acid, strikingly marks the main dorsal, but not ventral, nerve trunk after axon sorting at the limb plexus region. Our results suggest that EphA4 RTK and its ligands may influence axon fasciculation and the sorting of axons at the limb plexus, contributing to the correct dorsoventral organization of nerve branches in the hindlimb.
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Gene structure and expression study of the SEDL gene for Spondyloepiphyseal Dysplasia Tarda
(Academic Press Inc Elsevier Science, 2000) Gecz, J.; Hillman, M.; Gedeon, A.; Cox, T.; Baker, E.; Mulley, J.; Centre for the Molecular Genetics of Development
Spondyloepiphyseal dysplasia tarda (SEDL) is an X-linked recessive disorder of endochondral bone formation caused by mutations in the SEDL gene. Here we present the structural analysis and subcellular localization of human SEDL. The SEDL gene is composed of six exons and spans a genomic region of ~20 kb in Xp22. It contains four Alu sequences in its 3′ UTR and an alternatively spliced MER20 sequence in its 5′ UTR (exon 2). Complex alternative splicing was detected for exon 4. Altogether seven SEDL pseudogenes were detected in the human genome: SEDLP1, a transcribed retropseudogene (or retro-xaptonuon) on chromosome 19q13.4 with potential to encode a protein identical to that of the SEDL gene; SEDLP2, another retropseudogene (not transcribed) on chromosome 8; and five truncated pseudogenes, SEDLP3–SEDLP7, on chromosome Yq11.23. Based on the knowledge of the yeast SEDL ortholog we speculated that the SEDL protein may participate along the ER-to-Golgi transport compartments. To test this hypothesis we performed transient transfection studies with tagged recombinant mammalian SEDL proteins in Cos-7 cells. The tagged SEDL proteins localized to perinuclear structures that partly overlapped with the intermediate ER–Golgi compartment (ERGIC; or vesicular tubular complex, VTC). Two human SEDL mutations (157–158delAT and C271T(STOP)) introduced into SEDL FLAG and GFP constructs led to the misplacement of the SEDL protein primarily to the cell nucleus and partially to the cytoplasm. Based on these experiments we suggest that the COOH end of the SEDL protein might be responsible for proper targeting of SEDL along the ER–Golgi membrane compartments (including Golgi and ERGIC/VTC).
Open Access
Untying the Gordian knot of cytokinesis: role of small G proteins and their regulators
(Rockefeller Univ Press, 2000) Prokopenko, S.; Saint, R.; Bellen, H.; Centre for the Molecular Genetics of Development

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