Ratner Lab
Role of Merlin in Schwann Cells

Role of Merlin in Schwann Cells

Neurofibromatosis type 2 (NF2) gene mutation leads to schwannomas (Schwann cell tumors). Schwannomas account for 6 percent to 8 percent of intracranial neoplasms. Morbidity resulting from schwannomas can include nerve dysfunction and brainstem compression.

Merlin, the mutated gene in NF2 patients, encodes a membrane-cytoskeletal linking protein. We have shown dramatic cytoskeletal abnormalities in NF2 schwannomas (benign tumors comprised of Schwann cells). Using cellular human and mouse models of NF2, we aim to understand merlin’s role in Schwann cells. In 2019, Dr. Robert Hennigan extended this line of investigation, showing identifying Merlin-proximal proteins that are components of or associated with cell junctions and focal adhesions, using a technique called proximity biotinylation. He also identified a novel merlin-interacting protein, Tpbp53/Aspp2, which is under current investigation.

Related Publications

Hennigan, RF, Fletcher, J.S., Guard, S, and Ratner, N. Proximity biotinylation identifies a set of conformation-specific interactions between Merlin and cell junction proteins. Sci Signal. 2019 Apr 23;12(578).

Guo L, Moon C, Zheng Y, Ratner N. Cdc42 regulates Schwann cell radial sorting and myelin sheath folding through NF2/merlin-dependent and independent signaling. Glia. 2013 Nov;61(11):1906-21.

Hennigan RF, Moon CA, Parysek LM, Monk KR, Morfini G, Berth S, Brady S, Ratner N. The NF2 tumor suppressor regulates microtubule-based vesicle trafficking via a novel Rac, MLK and p38(SAPK) pathway. Oncogene. 2013 Feb 28;32(9):1135-43.

Guo L, Moon C, Niehaus K, Zheng Y, Ratner N. Rac1 controls Schwann cell myelination through cAMP and NF2/merlin. J Neurosci. 2012 Nov 28;32(48):17251-61.

Nakai Y, Zheng Y, MacCollin M, Ratner N. Temporal control of Rac in Schwann cell-axon interaction is disrupted in NF2-mutant schwannoma cells. J Neurosci. 2006 Mar 29;26(13):3390-5.

Bashour A, Meng J, Ip W, MacCollin M, Ratner N. The neurofibromatosis type 2 gene product, merlin, reverses the F-actin cytoskeletal defects in primary human Schwannoma cells. Mol Cell Biol. 2002 Feb;22(4):1150-7.

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Contact Us

For more information about the lab, contact Nancy Ratner, PhD, at  513-636-9469.