Interaction of voltage-gated sodium channels with the extracellular matrix molecules tenascin-C and tenascin-R

Proceedings of the National Academy of Sciences of the United States of America - Tập 95 Số 26 - Trang 15753-15757 - 1998
Jayashree Srinivasan1, Melitta Schachner1, William A. Catterall1
1Departments of Pharmacology and Neurological Surgery, University of Washington, Seattle, WA 98195-7280 and Zentrum für Molekulare Neurobiologie, University of Hamburg, Martinistrasse 52, D-20246 Hamburg, Germany

Tóm tắt

The type IIA rat brain sodium channel is composed of three subunits: a large pore-forming α subunit and two smaller auxiliary subunits, β1 and β2. The β subunits are single membrane-spanning glycoproteins with one Ig-like motif in their extracellular domains. The Ig motif of the β2 subunit has close structural similarity to one of the six Ig motifs in the extracellular domain of the cell adhesion molecule contactin (also called F3 or F11), which binds to the extracellular matrix molecules tenascin-C and tenascin-R. We investigated the binding of the purified sodium channel and the extracellular domain of the β2 subunit to tenascin-C and tenascin-R in vitro . Incubation of purified sodium channels on microtiter plates coated with tenascin-C revealed saturable and specific binding with an apparent K d of ≈15 nM. Glutathione S -transferase-tagged fusion proteins containing various segments of tenascin-C and tenascin-R were purified, digested with thrombin to remove the epitope tag, immobilized on microtiter dishes, and tested for their ability to bind purified sodium channel or the epitope-tagged extracellular domain of β2 subunits. Both purified sodium channels and the extracellular domain of the β2 subunit bound specifically to fibronectin type III repeats 1–2, A, B, and 6–8 of tenascin-C and fibronectin type III repeats 1–2 and 6–8 of tenascin-R but not to the epidermal growth factor-like domain or the fibrinogen-like domain of these molecules. The binding of neuronal sodium channels to extracellular matrix molecules such as tenascin-C and tenascin-R may play a crucial role in localizing sodium channels in high density at axon initial segments and nodes of Ranvier or in regulating the activity of immobilized sodium channels in these locations.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 95 Số 26

15753-15757

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