Peripheral Neuropathy Protein Interaction Network:

A significant proportion of peripheral neuropathies result from inadequate or deteriorating myelination of peripheral nerves. Such peripheral myelinopathies range in severity from Charcot-Marie-Tooth Disease (CMT), to more severe forms such as Dejerine Sottas disease (DS), and congenital hypomyelinating neuropathy (CHN). These myelination disorders constitute one of the most common types of human genetic disease, affecting more than 1 in 2500 individiuals. Tremendous progress has been made in identifying genetic causes of these diseases, but despite this progress, there are still a number of unanswered questions regarding how mutations in these genes cause human peripheral neuropathies. Unfortunately, the relatively small amount of peripheral nerve tissue hampers biochemical/proteomics analysis of neuropathy-associated proteins, and therefore investigating molecular function of these proteins is a challenge.

To address this challenge, we have initiated a project supported by the Muscular Dystrophy Association to identify networks of proteins that interact with those that have been found to be mutated in peripheral neuropathies. A protein interaction library was created from mouse sciatic nerve, which has been utilized by the Yeast Two Hybrid Facility at the University of Indiana to perform high-throughput yeast two-hybrid (Y2H) screens for proteins that interact with PMP22, MPZ, and several other proteins encoded by genes mutated in peripheral neuropathies. The data from these screens are summarized below to support further research into the molecular functions of these genes and open up new avenues for therapeutic intervention.

More information on CMT and related diseases can be found here:
Muscular Dystrophy Association
http://www.mda.org/disease/cmt.html
CMT Association
http://www.charcot-marie-tooth.org/about_cmt/overview.php
The National Institute of Neurological Disorders and Stroke at: http://www.ninds.nih.gov/disorders/charcot_marie_tooth/charcot_marie_tooth.htm

This project was supported by a grant from the Muscular Dystrophy Association, and also supported by the School of Veterinary Medicine and Waisman Center, University of Wisconsin.

Gene: LITAF

Y2H Screen Results for LITAF

Y2H Screen Summaryfor LITAF

CMT Mutation Search

Summary of Y2H Hits

Gene: EGR2

Y2H Screen Resultsfor EGR2

Y2H Screen Summary for EGR2

CMT Mutation Search

Summary of Y2H Hits

Gene: MTMR13

Y2H Screen Resultsfor MTMR13

Y2H Screen Summary for MTMR 13

Summary of Y2H Hits

Gene: MTMR2

Y2H Screen Results for MTMR2

Y2H Screen Summary for MTMR2

CMT Mutation Search

Summary of Y2H Hits

Gene: NEFL

Y2H Screen Results for NEFL

Y2H Screen Summary for NEFL

CMT Mutation Search

Summary of Y2H Hits

Gene : NDRG1

Y2H Screen Summary for NDRG1

Y2H Screen Results for NDRG1

CMT Mutation Search

Summary of Y2H Hits

Gene : Hyccin

Y2H Screen Resultsfor Hyccin

Y2H Screen Summaryfor Hyccin

CMT Mutation Search

Summary of Y2H Hits

Gene : PMP22

Y2H Screen Resultsfor PMP22

Y2H Screen Summaryfor PMP22

CMT Mutation Search

Summary of Y2H Hits

Gene : Periaxin

Y2H Screen Resultsfor Periaxin

Y2H Screen Summaryfor Periaxin

CMT Mutation Search

Summary of Y2H Hits

Gene : SH3TC2

Y2H Screen Results for SH3TC2

Y2H Screen Summary for SH3TC2

CMT Mutation Search

Summary of Y2H Hits

*Abbreviations: CMT, Charcot-Marie-Tooth; DSS, Dejerine Sottas Syndrome; CH, congenital hypomyelination; SH3TC2, SH3 domain and tetratricopeptide repeats 2