Universität zu Köln

Rademacher, Sebastian ORCID: 0000-0002-1592-9838, Verheijen, Bert M., Hensel, Niko, Peters, Miriam, Bora, Gamze, Brandes, Gudrun, de Sa, Renata Vieira, Heidrich, Natascha, Fischer, Silke, Brinkmann, Hella, van der Pol, W. Ludo, Wirth, Brunhilde ORCID: 0000-0003-4051-5191, Pasterkamp, R. Jeroen and Claus, Peter ORCID: 0000-0003-3824-9445 (2017). Metalloprotease-mediated cleavage of PlexinD1 and its sequestration to actin rods in the motoneuron disease spinal muscular atrophy (SMA). Hum. Mol. Genet., 26 (20). S. 3946 - 3960. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2083

Full text not available from this repository.

Abstract

Cytoskeletal rearrangement during axon growth is mediated by guidance receptors and their ligands which act either as repellent, attractant or both. Regulation of the actin cytoskeleton is disturbed in Spinal Muscular Atrophy (SMA), a devastating neurodegenerative disease affecting mainly motoneurons, but receptor-ligand interactions leading to the dysregulation causing SMA are poorly understood. In this study, we analysed the role of the guidance receptor PlexinD1 in SMA pathogenesis. We showed that PlexinD1 is cleaved by metalloproteases in SMA and that this cleavage switches its function from an attractant to repellent. Moreover, we found that the PlexinD1 cleavage product binds to actin rods, pathological aggregate-like structures which had so far been described for age-related neurodegenerative diseases. Our data suggest a novel disease mechanism for SMA involving formation of actin rods as a molecular sink for a cleaved PlexinD1 fragment leading to dysregulation of receptor signaling.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rademacher, Sebastian UNSPECIFIED orcid.org/0000-0002-1592-9838 UNSPECIFIED Verheijen, Bert M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hensel, Niko UNSPECIFIED UNSPECIFIED UNSPECIFIED Peters, Miriam UNSPECIFIED UNSPECIFIED UNSPECIFIED Bora, Gamze UNSPECIFIED UNSPECIFIED UNSPECIFIED Brandes, Gudrun UNSPECIFIED UNSPECIFIED UNSPECIFIED de Sa, Renata Vieira UNSPECIFIED UNSPECIFIED UNSPECIFIED Heidrich, Natascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Fischer, Silke UNSPECIFIED UNSPECIFIED UNSPECIFIED Brinkmann, Hella UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Pol, W. Ludo UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirth, Brunhilde UNSPECIFIED orcid.org/0000-0003-4051-5191 UNSPECIFIED Pasterkamp, R. Jeroen UNSPECIFIED UNSPECIFIED UNSPECIFIED Claus, Peter UNSPECIFIED orcid.org/0000-0003-3824-9445 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-214211
DOI:	10.1093/hmg/ddx282
Journal or Publication Title:	Hum. Mol. Genet.
Volume:	26
Number:	20
Page Range:	S. 3946 - 3960
Date:	2017
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2083
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MOTOR-NEURONS; MOUSE MODEL; MATRIX METALLOPROTEINASES; IMPAIRED ENDOCYTOSIS; NEURAL DEVELOPMENT; DETERMINING GENE; SEMAPHORIN 3E; AXON GROWTH; STEM-CELLS; EXPRESSION Multiple languages Biochemistry & Molecular Biology; Genetics & Heredity Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21421