TACE (ADAM17) inhibits Schwann cell myelination

Rosa La Marca, Federica Cerri, Keisuke Horiuchi, Angela Bachi, M. Laura Feltri, Lawrence Wrabetz, Carl P. Blobel, Angelo Quattrini, James L. Salzer, Carla Taveggia

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

Tumor necrosis factor-"converting enzyme (TACE; also known as ADAM17) is a proteolytic sheddase that is responsible for the cleavage of several membrane-bound molecules. We report that TACE cleaves neuregulin-1 (NRG1) type III in the epidermal growth factor domain, probably inactivating it (as assessed by deficient activation of the phosphatidylinositol-3-OH kinase pathway), and thereby negatively regulating peripheral nervous system (PNS) myelination. Lentivirus-mediated knockdown of TACE in vitro in dorsal root ganglia neurons accelerates the onset of myelination and results in hypermyelination. In agreement, motor neurons of conditional knockout mice lacking TACE specifically in these cells are significantly hypermyelinated, and small-caliber fibers are aberrantly myelinated. Further, reduced TACE activity rescues hypomyelination in NRG1 type III haploinsufficient mice in vivo. We also show that the inhibitory effect of TACE is neuron-autonomous, as Schwann cells lacking TACE elaborate myelin of normal thickness. Thus, TACE is a modulator of NRG1 type III activity and is a negative regulator of myelination in the PNS.

Original languageEnglish
Pages (from-to)857-865
Number of pages9
JournalNature Neuroscience
Volume14
Issue number7
DOIs
Publication statusPublished - 2011 Jul

Fingerprint

Neuregulin-1
Schwann Cells
Peripheral Nervous System
Neurons
Lentivirus
Spinal Ganglia
Motor Neurons
Myelin Sheath
Phosphatidylinositol 3-Kinases
Epidermal Growth Factor
Knockout Mice
Tumor Necrosis Factor-alpha
Membranes
ADAM17 Protein

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

La Marca, R., Cerri, F., Horiuchi, K., Bachi, A., Feltri, M. L., Wrabetz, L., ... Taveggia, C. (2011). TACE (ADAM17) inhibits Schwann cell myelination. Nature Neuroscience, 14(7), 857-865. https://doi.org/10.1038/nn.2849

TACE (ADAM17) inhibits Schwann cell myelination. / La Marca, Rosa; Cerri, Federica; Horiuchi, Keisuke; Bachi, Angela; Feltri, M. Laura; Wrabetz, Lawrence; Blobel, Carl P.; Quattrini, Angelo; Salzer, James L.; Taveggia, Carla.

In: Nature Neuroscience, Vol. 14, No. 7, 07.2011, p. 857-865.

Research output: Contribution to journalArticle

La Marca, R, Cerri, F, Horiuchi, K, Bachi, A, Feltri, ML, Wrabetz, L, Blobel, CP, Quattrini, A, Salzer, JL & Taveggia, C 2011, 'TACE (ADAM17) inhibits Schwann cell myelination', Nature Neuroscience, vol. 14, no. 7, pp. 857-865. https://doi.org/10.1038/nn.2849
La Marca R, Cerri F, Horiuchi K, Bachi A, Feltri ML, Wrabetz L et al. TACE (ADAM17) inhibits Schwann cell myelination. Nature Neuroscience. 2011 Jul;14(7):857-865. https://doi.org/10.1038/nn.2849
La Marca, Rosa ; Cerri, Federica ; Horiuchi, Keisuke ; Bachi, Angela ; Feltri, M. Laura ; Wrabetz, Lawrence ; Blobel, Carl P. ; Quattrini, Angelo ; Salzer, James L. ; Taveggia, Carla. / TACE (ADAM17) inhibits Schwann cell myelination. In: Nature Neuroscience. 2011 ; Vol. 14, No. 7. pp. 857-865.
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