Universität zu Köln

El-Awaad, Ehab, Pryymachuk, Galyna, Fried, Cora, Matthes, Jan ORCID: 0000-0003-2754-1555, Isensee, Joerg, Hucho, Tim, Neiss, Wolfram F., Paulsson, Mats, Herzig, Stefan, Zaucke, Frank and Pietsch, Markus (2019). Direct, gabapentin-insensitive interaction of a soluble form of the calcium channel subunit alpha(2)delta-1 with thrombospondin-4. Sci Rep, 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

The alpha(2)delta-1 subunit of voltage-gated calcium channels binds to gabapentin and pregabalin, mediating the analgesic action of these drugs against neuropathic pain. Extracellular matrix proteins from the thrombospondin (TSP) family have been identified as ligands of alpha(2)delta-1 in the CNS. This interaction was found to be crucial for excitatory synaptogenesis and neuronal sensitisation which in turn can be inhibited by gabapentin, suggesting a potential role in the pathogenesis of neuropathic pain. Here, we provide information on the biochemical properties of the direct TSP/alpha(2)delta-1 interaction using an ELISA-style ligand binding assay. Our data reveal that full-length pentameric TSP-4, but neither TSP-5/COMP of the pentamer-forming subgroup B nor TSP-2 of the trimer-forming subgroup A directly interact with a soluble variant of alpha(2)delta-1 (alpha(2)delta-1S). Interestingly, this interaction is not inhibited by gabapentin on a molecular level and is not detectable on the surface of HEK293-EBNA cells over-expressing alpha(2)delta-1 protein. These results provide biochemical evidence that supports a specific role of TSP-4 among the TSPs in mediating the binding to neuronal a2d-1 and suggest that gabapentin does not directly target TSP/alpha(2)delta-1 interaction to alleviate neuropathic pain.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code El-Awaad, Ehab UNSPECIFIED UNSPECIFIED UNSPECIFIED Pryymachuk, Galyna UNSPECIFIED UNSPECIFIED UNSPECIFIED Fried, Cora UNSPECIFIED UNSPECIFIED UNSPECIFIED Matthes, Jan UNSPECIFIED orcid.org/0000-0003-2754-1555 UNSPECIFIED Isensee, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucho, Tim UNSPECIFIED UNSPECIFIED UNSPECIFIED Neiss, Wolfram F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Paulsson, Mats UNSPECIFIED UNSPECIFIED UNSPECIFIED Herzig, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Zaucke, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Pietsch, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-128040
DOI:	10.1038/s41598-019-52655-y
Journal or Publication Title:	Sci Rep
Volume:	9
Date:	2019
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language OLIGOMERIC MATRIX PROTEIN; UP-REGULATION CONTRIBUTES; NEUROPATHIC PAIN STATES; MOLECULAR-CLONING; N-TYPE; SPINAL SENSITIZATION; EXPRESSION; CARTILAGE; NEURONS; SYNAPTOGENESIS Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12804