Distinct cellular and subcellular patterns of expression imply distinct functions for the Drosophila homologues of moesin and the neurofibromatosis 2 tumor suppressor, merlin.

McCartney, Brooke M.; Fehon, Richard G.

doi:10.1083/jcb.133.4.843

Cited by 147 publications

(136 citation statements)

References 44 publications

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“…The accumulation of Merlin at cell-to-cell junctions in confluent epithelial and endothelial cells [5,7], within lamellipodia in various types of cell [62][63][64], and on the surface of endocytic vesicles in Drosophila epithelial tissues [53,65] is consistent with this general hypothesis (Sidebar C).…”

Section: Merlin Localizationsupporting

confidence: 60%

Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus

et al. 2012

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Inhibition of proliferation by cell-to-cell contact is essential for tissue organization, and its disruption contributes to tumorigenesis. The FERM domain protein Merlin, encoded by the NF2 tumour suppressor gene, is an important mediator of contact inhibition. Merlin was thought to inhibit mitogenic signalling and activate the Hippo pathway by interacting with diverse target-effectors at or near the plasma membrane. However, recent studies highlight that Merlin pleiotropically affects signalling by migrating into the nucleus and inducing a growth-suppressive programme of gene expression through its direct inhibition of the CRL4 DCAF1 E3 ubiquitin ligase. In addition, Merlin promotes the establishment of epithelial adhesion and polarity by recruiting Par3 and aPKC to E-cadherin-dependent junctions, and by ensuring the assembly of tight junctions. These recent advances suggest that Merlin acts at the cell cortex and in the nucleus in a similar, albeit antithetic, manner to the oncogene β-catenin.

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Section: Merlin Localizationsupporting

confidence: 60%

Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus

et al. 2012

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“…Sequence analysis revealed that this gene represents the chick homolog of Nf2, a tumor suppressor gene, which had been identified previously in human (Rouleau et al, 1993;Trofatter et al, 1993), mouse (Haase et al, 1994;Claudio et al, 1994;Hara et al, 1994;Huynh et al, 1994), rat (Gutmann et al, 1995), and Drosophila (McCartney and Fehon, 1996). Analyses of the predicted amino acid sequence of c-merlin revealed protein domains in common with other identified merlin molecules ( Fig.…”

Section: Nf2 Cdna and Merlin Proteinsupporting

confidence: 52%

Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration

Chen

Gutmann

Haipek

et al. 2004

Developmental Dynamics

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The neurofibromatosis 2 (NF2) tumor suppressor protein merlin, or schwannomin, functions as a negative growth regulator such that inactivating mutations in Nf2 predispose humans to tumors. In addition, merlin has a critical role during embryonic development. Nf2-deficient mice die early during embryogenesis, with defects in gastrulation and extraembryonic tissues. To investigate the function of Nf2/merlin during embryonic development, we first identified the homologous Nf2 gene in chicken (cNf2) and examined the distribution of chicken merlin (c-merlin) during myogenesis. cNf2 encoded a full-length mRNA of 1,770 nucleotides and a protein of 589 residues. C-merlin shared high sequence homology and common protein motifs with vertebrate and Drosophila merlins. In addition, cNF2 functions as a negative growth regulator similar to human and Drosophila merlin in vitro. In vivo, c-merlin was expressed diffusely in the forming dermomyotome but down-regulated in migratory muscle precursors in the forelimb. As muscle formed in the limb, c-merlin expression was up-regulated. As an initial examination of c-merlin function during myogenesis, c-merlin was ectopically expressed in muscle precursors and the effects on muscle development were examined. We show that ectopic merlin expression reduces the proliferation of muscle precursors as well as their ability to migrate effectively in limb mesoderm. Collectively, these results demonstrate that c-merlin is developmentally regulated in migrating and differentiating myogenic cells, where it functions as a negative regulator of both muscle growth and motility. Developmental Dynamics 229:541-554, 2004.

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“…The Drosophila homolog of merlin shares sequence similarity to the human merlin protein (McCartney and Fehon, 1996;Fehon et al, 1997).…”

Section: Supplementary Notesmentioning

confidence: 99%

“…A phylogenetic study indicates that the FERM domains of ERM homologs from sea urchin, Caenorhabditis elegans, Drosophila melanogaster and vertebrates share 74-82% amino-acid identity and have about 60% identity with those of merlin [17,[28][29][30][31][32][33][34]. These levels of identity are exceptionally high, implying that the protein structure of the merlin and ERM proteins from these species may be well conserved.…”

Section: Caenorhabditis Elegansmentioning

confidence: 99%

The Role of Drosophila Merlin in the Control of Mitosis Exit and Development

Chang¹

2006

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Pu reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the dal, needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, Including suggestions for reducing this4urden to Department of Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-41o2. Respondents should be aware that notwithstanding any other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a currently valid 0MB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. REPORT DATE (DD-MM-YYYY)2. REPORT SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR'S ACRONYM(S) U.S. Army Medical Research and Materiel Command FortDetrick, Maryland 21702-5012 SPONSOR/MONITOR'S REPORT NUMBER(S)12. DISTRIBUTION / AVAILABILITY STATEMENT Approved for Public Release; Distribution Unlimited SUPPLEMENTARY NOTES14. ABSTRACT: Merlin, the NF2 gene product, shares a substantial homology with the ezrin-radixin-moesin (ERM) proteins. The merlin and ERM proteins are thought to be key regulators of interactions between the actin cytoskeleton and the plasma membrane in Schwann cells and polarized cells. They act as important members of signal transduction pathways that control cell growth and participate in the sorting of membrane proteins during exocytic traffic. Unlike ERM. Merlin has a distinct function as a tumor suppressor; however, the mechanism by which marline functions as a tumor suppressor is poorly understood. Drosophila melanogaster provides a genetic and developmental system that is amenable to experiment manipulation and has been very valuable to the study of tumor genetics. The Drosophila homolog of merlin shares sequence and functional similarity to the human protein. We have shown that merlin plays an important role in the control of mitosis exit and in the determination of dorsal/ventral compartment border during wing Imaginal disc development. Although merlin mutation did not seem to significantly affect the overall cell-cycle duration, merlin mutant displayed prolonged proliferation during the cell cycle. We showed that merlin is required for the determination of the wing morphology, and demonstrated a genetic interaction between merlin and porcupine, which controls the acetylation of the Wingless morphogen during the development of the wing imaginal disc. In addition, we showed a potential interaction between merlin and shibire, which is involved in wingless protein trafficking during early embryogenesis. Also, we found a role for merlin in spermatogenesis. Finally, we analyzed the origin and evolution of merlin, and identified a monophyletic origin of the merlin prot...

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Distinct cellular and subcellular patterns of expression imply distinct functions for the Drosophila homologues of moesin and the neurofibromatosis 2 tumor suppressor, merlin.

Cited by 147 publications

References 44 publications

Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus

Merlin: a tumour suppressor with functions at the cell cortex and in the nucleus

Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration

The Role of Drosophila Merlin in the Control of Mitosis Exit and Development

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