[en] Charcot-Marie-Tooth (CMT) diseases are a heterogeneous group of genetic peripheral neuropathies caused by mutations in a variety of genes, which are involved in the development and maintenance of peripheral nerves. Myelin protein zero (MPZ) is expressed by Schwann cells, and MPZ mutations can lead to primarily demyelinating polyneuropathies including CMT type 1B. Different mutations demonstrate various forms of disease pathomechanisms, which may be beneficial in understanding the disease cellular pathology. Our molecular dynamics simulation study on the possible impacts of I30T mutation on the MPZ protein structure suggested a higher hydrophobicity and thus lower stability in the membranous structures. A study was also conducted to predict native/mutant MPZ interactions. To validate the results of the simulation study, the native and mutant forms of the MPZ protein were separately expressed in a cellular model, and the protein trafficking was chased down in a time course pattern. In vitro studies provided more evidence on the instability of the MPZ protein due to the mutation. In this study, qualitative and quantitative approaches were adopted to confirm the instability of mutant MPZ in cellular membranes.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Ghanavatinejad, Fatemeh ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques ; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Science, Shahrekord, Iran
Pourteymourfard-Tabrizi, Zahra; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Science, Shahrekord, Iran
Mahnam, Karim; Department of Biology, Faculty of Science, Shahrekord University, Rahbar Blvd, Shahrekord, Chaharmahal and Bakhtiari Province, Iran
Doosti, Abbas; Biotechnology Research Center, School of Basic Sciences, Islamic Azad University, Shahrekord Branch, Rahmatieh, Shahrekord, Chaharmahal and Bakhtiari Province, Iran
Mehri-Ghahfarrokhi, Ameneh; Department of Molecular Medicine, School of Advanced Technologies, Shahrekord University of Medical Sciences, Rahmatieh, Shahrekord, Chaharmahal and Bakhtiari Province, Iran
Pourhadi, Masoumeh; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Science, Shahrekord, Iran
Azimeh Hosseini, Sayedeh; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Science, Shahrekord, Iran
Hashemzadeh Chaleshtori, Morteza; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Science, Shahrekord, Iran
Soltanzadeh, Payam; Department of Neurology, David Geffen School of Medicine, University of California Los Angeles (UCLA), 710 Westwood Plaza, Los Angeles, California, 90095, USA
Jami, Mohammad-Saeid; Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Science, Shahrekord, Iran ; Department of Neurology, David Geffen School of Medicine, University of California Los Angeles (UCLA), 710 Westwood Plaza, Los Angeles, California, 90095, USA
Language :
English
Title :
In silico and in vitro effects of the I30T mutation on myelin protein zero instability in the cell membrane.
We thank all the staff and faculty members who helped us at SKUMS. This study was financially supported by the Shahrekord University of Medical Sciences, Iran (Grant Number 803).
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