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Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion molecule L1 to promote neuronal and Schwann cell migration as well as myelination

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Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion molecule L1 to promote neuronal and Schwann cell migration as well as myelination. / Lutz, David; Wolters-Eisfeld, Gerrit; Schachner, Melitta; Kleene, Ralf.

In: J NEUROCHEM, Vol. 128, No. 5, 01.03.2014, p. 713-24.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Lutz, D, Wolters-Eisfeld, G, Schachner, M & Kleene, R 2014, 'Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion molecule L1 to promote neuronal and Schwann cell migration as well as myelination', J NEUROCHEM, vol. 128, no. 5, pp. 713-24. https://doi.org/10.1111/jnc.12473

APA

Lutz, D., Wolters-Eisfeld, G., Schachner, M., & Kleene, R. (2014). Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion molecule L1 to promote neuronal and Schwann cell migration as well as myelination. J NEUROCHEM, 128(5), 713-24. https://doi.org/10.1111/jnc.12473

Vancouver

Lutz D, Wolters-Eisfeld G, Schachner M, Kleene R. Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion molecule L1 to promote neuronal and Schwann cell migration as well as myelination. J NEUROCHEM. 2014 Mar 1;128(5):713-24. https://doi.org/10.1111/jnc.12473

Bibtex

@article{c2266587282c4fd98855ba8571522f09,
title = "Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion molecule L1 to promote neuronal and Schwann cell migration as well as myelination",
abstract = "The cell adhesion molecule L1 regulates cellular responses in the developing and adult nervous system. Here, we show that stimulation of cultured mouse cerebellar neurons by a function-triggering L1 antibody leads to cathepsin E-mediated generation of a sumoylated 30 kDa L1 fragment (L1-30) and to import of L1-30 into the nucleus. Mutation of the sumoylation site at K1172 or the cathepsin E cleavage site at E1167 abolishes generation of L1-30, while mutation of the nuclear localization signal at K1147 prevents nuclear import of L1-30. Moreover, the aspartyl protease inhibitor pepstatin impairs the generation of L1-30 and inhibits L1-induced migration of cerebellar neurons and Schwann cells as well as L1-dependent in vitro myelination on axons of dorsal root ganglion neurons by Schwann cells. L1-stimulated migration of HEK293 cells expressing L1 with mutated cathepsin E cleavage site is diminished in comparison to migration of cells expressing non-mutated L1. In addition, L1-stimulated migration of HEK293 cells expressing non-mutated L1 is also abolished upon knock-down of cathepsin E expression and enhanced by over-expression of cathepsin E. The findings of the present study indicate that generation and nuclear import of L1-30 regulate neuronal and Schwann cell migration as well as myelination. Cell adhesion molecule L1 regulates cellular responses in the developing and adult nervous system. L1 stimulation triggers sumoylation and cleavage of L1, thus generating the L1-70 fragment (1) which is cleaved by cathepsin E (2) yielding the L1-30 fragment that is imported to the nucleus (3), may bind to DNA and/or nuclear proteins (4), to regulate diverse cellular functions.",
keywords = "Animals, Axons, Cathepsin E, Cell Movement, Cerebellum, Coculture Techniques, HEK293 Cells, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Mutagenesis, Site-Directed, Mutation, Myelin Sheath, Neural Cell Adhesion Molecule L1, Neurites, Neurons, Pepstatins, Peptide Fragments, Protease Inhibitors, RNA, Small Interfering, Schwann Cells, Sumoylation",
author = "David Lutz and Gerrit Wolters-Eisfeld and Melitta Schachner and Ralf Kleene",
note = "{\textcopyright} 2013 International Society for Neurochemistry.",
year = "2014",
month = mar,
day = "1",
doi = "10.1111/jnc.12473",
language = "English",
volume = "128",
pages = "713--24",
journal = "J NEUROCHEM",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "5",

}

RIS

TY - JOUR

T1 - Cathepsin E generates a sumoylated intracellular fragment of the cell adhesion molecule L1 to promote neuronal and Schwann cell migration as well as myelination

AU - Lutz, David

AU - Wolters-Eisfeld, Gerrit

AU - Schachner, Melitta

AU - Kleene, Ralf

N1 - © 2013 International Society for Neurochemistry.

PY - 2014/3/1

Y1 - 2014/3/1

N2 - The cell adhesion molecule L1 regulates cellular responses in the developing and adult nervous system. Here, we show that stimulation of cultured mouse cerebellar neurons by a function-triggering L1 antibody leads to cathepsin E-mediated generation of a sumoylated 30 kDa L1 fragment (L1-30) and to import of L1-30 into the nucleus. Mutation of the sumoylation site at K1172 or the cathepsin E cleavage site at E1167 abolishes generation of L1-30, while mutation of the nuclear localization signal at K1147 prevents nuclear import of L1-30. Moreover, the aspartyl protease inhibitor pepstatin impairs the generation of L1-30 and inhibits L1-induced migration of cerebellar neurons and Schwann cells as well as L1-dependent in vitro myelination on axons of dorsal root ganglion neurons by Schwann cells. L1-stimulated migration of HEK293 cells expressing L1 with mutated cathepsin E cleavage site is diminished in comparison to migration of cells expressing non-mutated L1. In addition, L1-stimulated migration of HEK293 cells expressing non-mutated L1 is also abolished upon knock-down of cathepsin E expression and enhanced by over-expression of cathepsin E. The findings of the present study indicate that generation and nuclear import of L1-30 regulate neuronal and Schwann cell migration as well as myelination. Cell adhesion molecule L1 regulates cellular responses in the developing and adult nervous system. L1 stimulation triggers sumoylation and cleavage of L1, thus generating the L1-70 fragment (1) which is cleaved by cathepsin E (2) yielding the L1-30 fragment that is imported to the nucleus (3), may bind to DNA and/or nuclear proteins (4), to regulate diverse cellular functions.

AB - The cell adhesion molecule L1 regulates cellular responses in the developing and adult nervous system. Here, we show that stimulation of cultured mouse cerebellar neurons by a function-triggering L1 antibody leads to cathepsin E-mediated generation of a sumoylated 30 kDa L1 fragment (L1-30) and to import of L1-30 into the nucleus. Mutation of the sumoylation site at K1172 or the cathepsin E cleavage site at E1167 abolishes generation of L1-30, while mutation of the nuclear localization signal at K1147 prevents nuclear import of L1-30. Moreover, the aspartyl protease inhibitor pepstatin impairs the generation of L1-30 and inhibits L1-induced migration of cerebellar neurons and Schwann cells as well as L1-dependent in vitro myelination on axons of dorsal root ganglion neurons by Schwann cells. L1-stimulated migration of HEK293 cells expressing L1 with mutated cathepsin E cleavage site is diminished in comparison to migration of cells expressing non-mutated L1. In addition, L1-stimulated migration of HEK293 cells expressing non-mutated L1 is also abolished upon knock-down of cathepsin E expression and enhanced by over-expression of cathepsin E. The findings of the present study indicate that generation and nuclear import of L1-30 regulate neuronal and Schwann cell migration as well as myelination. Cell adhesion molecule L1 regulates cellular responses in the developing and adult nervous system. L1 stimulation triggers sumoylation and cleavage of L1, thus generating the L1-70 fragment (1) which is cleaved by cathepsin E (2) yielding the L1-30 fragment that is imported to the nucleus (3), may bind to DNA and/or nuclear proteins (4), to regulate diverse cellular functions.

KW - Animals

KW - Axons

KW - Cathepsin E

KW - Cell Movement

KW - Cerebellum

KW - Coculture Techniques

KW - HEK293 Cells

KW - Humans

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Mutagenesis, Site-Directed

KW - Mutation

KW - Myelin Sheath

KW - Neural Cell Adhesion Molecule L1

KW - Neurites

KW - Neurons

KW - Pepstatins

KW - Peptide Fragments

KW - Protease Inhibitors

KW - RNA, Small Interfering

KW - Schwann Cells

KW - Sumoylation

U2 - 10.1111/jnc.12473

DO - 10.1111/jnc.12473

M3 - SCORING: Journal article

C2 - 24118054

VL - 128

SP - 713

EP - 724

JO - J NEUROCHEM

JF - J NEUROCHEM

SN - 0022-3042

IS - 5

ER -