Disease relevance of Nf2

• These findings contrast with data reported previously for human mesotheliomas, in which the NF2 gene was found to be mutated in 40% of cases [1].
• Individuals affected with NF2 develop schwannomas at an increased frequency [2].
• Neurofibromatosis type 2, a disease characterized by the formation of multiple nervous system tumors, especially schwannomas, is caused by mutation in the gene-encoding merlin/schwannomin [3].

High impact information on Nf2

• Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L [4].
• Functional analysis of neurofibromatosis 2 (NF2) missense mutations [5].
• To determine the role of this important negative growth regulator during normal embryonic development, the expression of these two merlin isoforms was examined at representative stages of rat embryogenesis and in adult tissues [6].
• The neurofibromatosis 2 (NF2) gene product, merlin, encodes a 595 amino acid protein with sequence similarity to a family of proteins linking cell membrane proteins to the cytoskeleton [6].
• Expression of the neurofibromatosis 2 (NF2) gene isoforms during rat embryonic development [6].

Chemical compound and disease context of Nf2

• To investigate the role of this tumor suppressor gene in rat asbestos-induced mesothelioma, a commonly used model for the human disease, we characterized the rat homologue of NF2 and examined rat chrysotile-induced primary mesotheliomas and cell lines derived from chrysotile- and crocidolite-induced mesotheliomas for alterations in this gene [1].

Biological context of Nf2

• Nf2-deficient mice die early during embryogenesis, with defects in gastrulation and extraembryonic tissues [7].
• The elucidation of the pattern of merlin gene expression in adult and embryonic tissues provides the foundations for future studies aimed at determining the function(s) of this protein during cell differentiation and embryonic development [6].
• C-merlin shared high sequence homology and common protein motifs with vertebrate and Drosophila merlins [7].
• Reverse transcription-polymerase chain reaction analysis to examine splicing of NF2 exons in mesothelioma cells indicated that the exon splicing pattern was similar in normal and neoplastic cells [1].
• Characterization of chicken Nf2/merlin indicates regulatory roles in cell proliferation and migration [7].

Anatomical context of Nf2

• The colocalization of ERM proteins with actin indicates that they have functions different from those of merlin in myelinating Schwann cells [8].
• In situ hybridization and RT-PCR analyses demonstrated that rat merlin is widely expressed during embryogenesis and early postnatal life in most tissues but becomes restricted to the brainstem, cerebellum, dorsal root ganglia, spinal cord, adrenal gland and testis in adult animals [6].
• Analysis of molecular domains of epitope-tagged merlin isoforms in Cos-7 cells and primary rat Schwann cells [9].
• In addition, the over-expressed merlin localizes to other actin-rich cortical structures, such as microvilli and filopodia [9].
• However, distinct from the ERM proteins, the carboxy-terminal-truncated merlin and F-actin do not co-localize with each other at the stress fibers [9].

Associations of Nf2 with chemical compounds

• Although C3T caused dose-dependent morphological abnormalities, FAK, paxillin, and schwannomin were able to coimmunoprecipitate with beta(1) integrin [10].

Other interactions of Nf2

• Merlin, the neurofibromatosis type 2 gene product, and beta1 integrin associate in isolated and differentiating Schwann cells [3].

Analytical, diagnostic and therapeutic context of Nf2

• Partial sequence analysis of the rat merlin gene demonstrated striking amino acid identity to the published mouse and human merlin gene sequences [6].
• In Schwann cell/sensory neuron cocultures, beta(1) integrins complex with focal adhesion kinase (FAK), fyn kinase, paxillin, and schwannomin in response to basal lamina adhesion [10].
• Western blot analysis of soluble and insoluble culture fractions demonstrated that the majority of merlin and related proteins were soluble in isolated SCs and undifferentiated SC/N cultures, but became insoluble in myelinating SC/N cultures [3].
• Double immunofluorescence staining suggested that merlin translocated from the perinuclear cytoplasm in undifferentiated SCs to the subplasmalemma in differentiating SCs and partially colocalized with beta1 integrin [3].
• In this paper, we report that merlin is expressed in Schwann cells, where it is localized in vitro to the cell membrane by immunohistochemistry and subcellular fractionation [2].

References