Open Close
Reference
Citation
Abeysundara, N., Leung, A.C., Primrose, D.A., Hughes, S.C. (2014). Regulation of cell proliferation and adhesion by means of a novel region of drosophila merlin interacting with Sip1.  Dev. Dyn. 243(12): 1554--1570.
FlyBase ID
FBrf0226713
Publication Type
Research paper
Abstract

The tumor suppressor protein merlin is thought to regulate cell proliferation and cell adhesion through interaction with protein partners. Loss of merlin is associated with Neurofibromatosis Type 2 (NF2) tumors. NHERF1 or EBP50 is a scaffolding protein that functions in apical organization of polarized cells. Merlin and NHERF1 have been shown to interact in vitro in vertebrates. We investigate how the Drosophila NHERF1 orthologue, Sip1, and Merlin function to regulate cell proliferation and adhesion. We identify two conserved arginine residues (R325 and R335) in Merlin which, in addition to the FERM domain, are required for interaction with Sip1. Mutation of the arginine residues result in reduced Sip1 binding to Merlin and loss of Merlin growth suppressor function. Over-expression of Merlin(R325A) and/or Merlin(R335L) in Drosophila wings result in increased proliferation in the adult wing (increase in size), which is rescued by co-over-expression of constitutively active Merlin protein. Reduced Sip1 binding to Merlin also produces defects in adhesion in follicle epithelial cells. Sip1 facilitates the activation of Merlin as a tumor suppressor protein. Thus, our work provides insight into how Merlin functions as a tumor suppressor and in adhesion and this provides insight into the mechanism of NF2 pathogenesis. Developmental Dynamics 243:1554-1570 , 2014. © 2014 Wiley Periodicals, Inc.

PubMed ID
PubMed Central ID
Associated Information
Comments
Associated Files
Other Information
Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Dev. Dyn.
    Title
    Developmental Dynamics
    Publication Year
    1992-
    ISBN/ISSN
    1058-8388
    Data From Reference
    Alleles (12)
    Genes (3)
    Human Disease Models (1)
    Physical Interactions (3)
    Cell Lines (1)
    Natural transposons (1)
    Experimental Tools (2)
    Transgenic Constructs (9)