A dual role for Integrin α6β4 in modulating hereditary neuropathy with liability to pressure palsies

Y Poitelon, V Matafora, N Silvestri, D Zambroni, C McGarry, N Serghany, T Rush, D Vizzuso, FA Court, A Bachi, L Wrabetz, ML Feltri

Research output: Contribution to journalArticle

Abstract

Peripheral myelin protein 22 (PMP22) is a component of compact myelin in the peripheral nervous system. The amount of PMP22 in myelin is tightly regulated, and PMP22 over or under-expression cause Charcot-Marie-Tooth 1A (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP). Despite the importance of PMP22, its function remains largely unknown. It was reported that PMP22 interacts with the β4 subunit of the laminin receptor α6β4 integrin, suggesting that α6β4 integrin and laminins may contribute to the pathogenesis of CMT1A 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 PMP22 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. (Figure presented.). © 2018 International Society for Neurochemistry
Original languageEnglish
Pages (from-to)245-257
Number of pages13
JournalJournal of Neurochemistry
Volume145
Issue number3
DOIs
Publication statusPublished - 2018

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Myelin Proteins
Integrins
Paralysis
Myelin Sheath
Pressure
Schwann Cells
Cells
Laminin Receptors
Neurochemistry
Charcot-Marie-Tooth Disease
Protein Stability
Neural Conduction
Peripheral Nervous System
Neurology
Laminin
Ablation
Tomaculous neuropathy
Tooth
Animals
Fibers

Cite this

A dual role for Integrin α6β4 in modulating hereditary neuropathy with liability to pressure palsies. / Poitelon, Y; Matafora, V; Silvestri, N; Zambroni, D; McGarry, C; Serghany, N; Rush, T; Vizzuso, D; Court, FA; Bachi, A; Wrabetz, L; Feltri, ML.

In: Journal of Neurochemistry, Vol. 145, No. 3, 2018, p. 245-257.

Research output: Contribution to journalArticle

Poitelon, Y, Matafora, V, Silvestri, N, Zambroni, D, McGarry, C, Serghany, N, Rush, T, Vizzuso, D, Court, FA, Bachi, A, Wrabetz, L & Feltri, ML 2018, 'A dual role for Integrin α6β4 in modulating hereditary neuropathy with liability to pressure palsies', Journal of Neurochemistry, vol. 145, no. 3, pp. 245-257. https://doi.org/10.1111/jnc.14295
Poitelon, Y ; Matafora, V ; Silvestri, N ; Zambroni, D ; McGarry, C ; Serghany, N ; Rush, T ; Vizzuso, D ; Court, FA ; Bachi, A ; Wrabetz, L ; Feltri, ML. / A dual role for Integrin α6β4 in modulating hereditary neuropathy with liability to pressure palsies. In: Journal of Neurochemistry. 2018 ; Vol. 145, No. 3. pp. 245-257.
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abstract = "Peripheral myelin protein 22 (PMP22) is a component of compact myelin in the peripheral nervous system. The amount of PMP22 in myelin is tightly regulated, and PMP22 over or under-expression cause Charcot-Marie-Tooth 1A (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP). Despite the importance of PMP22, its function remains largely unknown. It was reported that PMP22 interacts with the β4 subunit of the laminin receptor α6β4 integrin, suggesting that α6β4 integrin and laminins may contribute to the pathogenesis of CMT1A 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 PMP22 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. (Figure presented.). {\circledC} 2018 International Society for Neurochemistry",
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AU - Matafora, V

AU - Silvestri, N

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AU - McGarry, C

AU - Serghany, N

AU - Rush, T

AU - Vizzuso, D

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AB - Peripheral myelin protein 22 (PMP22) is a component of compact myelin in the peripheral nervous system. The amount of PMP22 in myelin is tightly regulated, and PMP22 over or under-expression cause Charcot-Marie-Tooth 1A (CMT1A) and Hereditary Neuropathy with Pressure Palsies (HNPP). Despite the importance of PMP22, its function remains largely unknown. It was reported that PMP22 interacts with the β4 subunit of the laminin receptor α6β4 integrin, suggesting that α6β4 integrin and laminins may contribute to the pathogenesis of CMT1A 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 PMP22 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. (Figure presented.). © 2018 International Society for Neurochemistry

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