Merlin differentially associates with the microtubule and actin cytoskeleton

Xu, Hua-mei; Gutmann, David H.

doi:10.1002/(sici)1097-4547(19980201)51:3<403::aid-jnr13>3.0.co;2-7

Cited by 157 publications

(86 citation statements)

References 30 publications

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“…Merlin can bind actin either directly through lowaffinity binding sites reported in the FERM domain (residues 178-367) (Xu and Gutmann, 1998;Brault et al, 2001;James et al, 2001), or indirectly via the actin binding protein b-fodrin/bII-spectrin (Scoles et al, 1998;Neill and Crompton, 2001). Merlin is detergent (Triton X-100)-insoluble, which is indicative of its capability to interact with the cytoskeleton (Deguen et al, 1998;Stokowski and Cox, 2000).…”

Section: Magicin Associates With the Actin Cytoskeletonmentioning

confidence: 99%

“…Merlin interacts with F-actin through actin binding sites within the FERM domain (Xu and Gutmann, 1998;Brault et al, 2001;James et al, 2001). In addition to actin, several other merlin interacting proteins have been identified, which include b-fodrin/bII-spectrin (Scoles et al, 1998;Neill and Crompton, 2001), SCHIP-1 (Goutebroze et al, 2000), NHE-RF (Murthy et al, 1998), b1-integrin (Obremski et al, 1998), CD44 (Sainio et al, 1997;Morrison et al, 2001), HRS (Scoles et al, 2000), RhoGDI (Maeda et al, 1999), syntenin (Jannatipour et al, 2001), paxillin (Fernandez-Valle et al, 2002) and RIb subunit of the cAMP-protein kinase A (Gronholm et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

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Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2

et al. 2004

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Neurofibromatosis 2 (NF2) is a dominantly inherited disorder characterized by bilateral vestibular schwannomas and meningiomas. Merlin, the neurofibromatosis 2 tumor suppressor protein, is related to the ERM (ezrin, radixin, moesin) proteins and, like its family members, is thought to play a role in plasma membrane-cytoskeletal interactions. We report a novel protein as a merlin-specific binding partner that we have named magicin (merlin and Grb2 interacting cytoskeletal protein) and show that the two proteins interact in vitro and in vivo as well as colocalize beneath the plasma membrane. Magicin is a 24 kDa protein that is expressed in many cell lines and tissues. Magicin, similar to merlin, associates with the actin cytoskeleton as determined by cofractionation, immunofluorescence and electron microscopy. Analysis of the magicin sequence reveals binding motifs for the adaptor protein Grb2. Employing affinity binding, blot overlay and co-immunoprecipitation assays, we demonstrate an interaction between Grb2 and magicin. In addition, merlin is capable of forming a ternary complex with magicin and Grb2. These results support a role for merlin in receptor-mediated signaling at the cell surface, and may have implications in the regulation of cytoskeletal reorganization.

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Section: Magicin Associates With the Actin Cytoskeletonmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2

et al. 2004

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“…The NF2 gene encodes a 595 amino-acid protein Merlin (schwannomin), which is related to the Ezrin-Radixin-Moesin (ERM) protein family and was hence dubbed Merlin for Moesin, Ezrin, Radixin-like protein (Rouleau et al, 1993;Trofatter et al, 1993). Merlin is putative tumor suppressor that is anchored at cell membrane where it links transmembrane receptors to the actin cytoskeleton (Xu and Gutmann, 1998;den Bakker et al, 2000). Merlin can form homo-and heterotypic interactions which in turn regulate its binding to other proteins.…”

Section: Introductionmentioning

confidence: 99%

VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation

Huang

Chen

2008

Oncogene

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Inactivation of the neurofibromatosis type 2 (NF2) tumor suppressor gene function has been observed not only in familial schwannomas and other central nervous system tumors, but also in malignant tumors unrelated to the NF2 syndrome, indicating a broader role of NF2 in human tumorigenesis. The NF2-encoded protein Merlin is closely related to the Ezrin-Radixin-Moesin family of membrane/ cytoskeleton linker proteins, and has been demonstrated to suppress tumor growth by inhibiting extracellular signal-regulated kinase (ERK) and Rac1 activation. Interestingly, serum deprivation has been shown to regulate Merlin at the protein level, however, exactly how such condition affects Merlin remains elusive. In this study, we provide evidence to show that Merlin is regulated in a Roc1-Cullin4A-DDB1-dependent manner. Following serum stimulation, Merlin is recruited to the E3 ligase complex through a direct interaction with the WD40-containing adaptor protein VprBP. Loading of Merlin to the E3 ubiquitin ligase complex resulted in its polyubiquitination, and consequently its proteasomemediated degradation. Consistently, VprBP depletion abolished the in vivo interaction of Merlin and Roc1-Cullin4A-DDB1, which resulted in Merlin stabilization and inhibited ERK and Rac activation. Together, our data revealed a novel regulatory mechanism for the tumor suppressor function of Merlin.

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“…The unique C-terminus of merlin lacks the conventional actin-binding domain found in the ERM proteins. However, merlin can directly binds actin using the residues at the N-terminal domain and indirectly through its association with 0311-spectrin or fodrin [14][15][16]. 21 The merlin and ERM proteins are thought to be key regulators of interactions between the actin cytoskeleton and the plasma membrane in polarized cells.…”

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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Merlin differentially associates with the microtubule and actin cytoskeleton

Cited by 157 publications

References 30 publications

Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2

Magicin, a novel cytoskeletal protein associates with the NF2 tumor suppressor merlin and Grb2

VprBP targets Merlin to the Roc1-Cul4A-DDB1 E3 ligase complex for degradation

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

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