title: Signaling proteins in the axoglial apparatus of sciatic nerve nodes of Ranvier.
abstract: During action potential conduction, the axonal specializations at the node, together with the adjacent paranodal terminations of the myelin sheath, interact with glial processes that invest the nodal gap. The nature of the mutual signals between axons and myelinating glia, however, are not well understood. Here we have characterized the distribution of inositol 1,4,5-trisphosphate receptors (IP(3)Rs) in the axoglial apparatus by immunohistochemistry, using known myelin domain-specific markers. While IP(3)R1 is not expressed in the Schwann cells or the axon, IP(3)R2 and IP(3)R3 are expressed in distinct cellular domains, suggesting distinct signaling roles for the two receptors. IP(3)R3 is the most predominant isoform in Schwann cells, and is expressed in particularly dense patches in the paranodal region. In addition to IP(3)Rs, two other members of the metabotropic Ca(2+) signaling pathway, G(alpha)q, and P(2)Y1 type of purinoceptors were also found in Schwann cells. Their pattern of expression matches the expression of their signaling partners, the IP(3)Rs. One interesting finding to emerge from this study is the expression of connexin 32 (Cx32) in close proximity with IP(3)R3. Although IP(3)R3 and Cx32 are not colocalized, their expression in the same membrane areas raises the question whether Schwann cell Ca(2+) signals either control the function of the gap junctions, or whether the gap junctional channels serve as conduits for rapid radial spread of Ca(2+) signals initiated during action potential propagation.
authors.affiliation: Section on Cell Biology and Signal Transduction, NICHD, NIH, Bethesda, Maryland 20892-4480, USA.
authors.forename: Joanna C
authors.initials: JC
authors.lastname: Toews
authors.forename: Vincent
authors.initials: V
authors.lastname: Schram
authors.forename: Susanna H
authors.initials: SH
authors.lastname: Weerth
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Mignery
authors.forename: James T
authors.initials: JT
authors.lastname: Russell
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D020013:Calcium Signaling / Q000502:physiology; D017630:Connexins / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D020033:Protein Isoforms / Q000378:metabolism; D011901:Ranvier's Nodes / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1; D012583:Schwann Cells / Q000378:metabolism* / Q000648:ultrastructure; D012584:Sciatic Nerve / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology*; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D053496:Inositol 1,4,5-Trisphosphate Receptors; D020033:Protein Isoforms; D018048:Receptors, Purinergic P2; D058472:Receptors, Purinergic P2Y1; D000097002:Gap Junction beta-1 Protein; C506928:ITPR2 protein, rat; C506929:ITPR3 protein, human; C546382:P2RY1 protein, human; C546384:P2ry1 protein, rat