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A dual role for Integrin α6β4 in modulating hereditary neuropathy with liability to pressure palsies
Author(s) -
Poitelon Yannick,
Matafora Vittoria,
Silvestri Nicholas,
Zambroni Desirée,
McGarry Claire,
Serghany Nora,
Rush Thomas,
Vizzuso Domenica,
Court Felipe A.,
Bachi Angela,
Wrabetz Lawrence,
Feltri Maria Laura
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14295
Subject(s) - integrin , myelin , laminin , peripheral myelin protein 22 , microbiology and biotechnology , extracellular matrix , peripheral nervous system , neuroscience , biology , receptor , pathology , chemistry , medicine , central nervous system , genetics
Peripheral myelin protein 22 ( PMP 22) is a component of compact myelin in the peripheral nervous system. The amount of PMP 22 in myelin is tightly regulated, and PMP 22 over or under‐expression cause Charcot‐Marie‐Tooth 1A ( CMT 1A) and Hereditary Neuropathy with Pressure Palsies ( HNPP ). Despite the importance of PMP 22 , its function remains largely unknown. It was reported that PMP 22 interacts with the β4 subunit of the laminin receptor α6β4 integrin, suggesting that α6β4 integrin and laminins may contribute to the pathogenesis of CMT 1A or HNPP . Here we asked if the lack of α6β4 integrin in Schwann cells influences myelin stability in the HNPP mouse model. Our data indicate that PMP 22 and β4 integrin may not interact directly in myelinating Schwann cells, however, ablating β4 integrin delays the formation of tomacula, a characteristic feature of HNPP . In contrast, ablation of integrin β4 worsens nerve conduction velocities and non‐compact myelin organization in HNPP animals. This study demonstrates that indirect interactions between an extracellular matrix receptor and a myelin protein influence the stability and function of myelinated fibers.