Cloning of a new gap junction gene (Cx36) highly expressed in mammalian brain neurons

Condorelli, D. F.; Parenti, Rosalba; Spinella, Francesca; Salinaro, Angela Trovato; Belluardo, Natale; Cardile, Venera; Cicirata, F

doi:10.1046/j.1460-9568.1998.00163.x

Cited by 434 publications

(364 citation statements)

References 23 publications

Supporting

Mentioning

331

Contrasting

Unclassified

Order By: Relevance

“…Thus, these gap junctions must be comprised of other connexins. That is not surprising, as connexin 36 is predominantly or exclusively found in neurons (Condorelli et al, 1998Belluardo et al, 2000;Rash et al, 2001), and connexin 43 is known to be present in the olfactory nerve layer (Paternostro et al, 1995).…”

Section: Discussionmentioning

confidence: 94%

Intercellular interactions in the mammalian olfactory nerve

Blinder

Pumplin

Paul

et al. 2003

J of Comparative Neurology

View full text Add to dashboard Cite

The small, unmyelinated axons of olfactory sensory neurons project to the olfactory bulb in densely packed fascicles, an arrangement conducive to axo-axonal interactions. We recently demonstrated ephaptic interactions between these axons in the olfactory nerve layer, the layer of the olfactory bulb in which the axon fascicles interweave and rearrange extensively. In the present study, we hypothesized that the axons, which express connexins, may have another mode of communication: gap junctions. Previous transmission electron microscopy (TEM) studies have failed to demonstrate such junctions. However, the definitive method for detecting gap junctions, freeze fracture, has not been used to examine the interaxonal connections of the olfactory nerve layer. Here, we apply a combined approach of TEM and freeze fracture to determine if gap junctions are present between the olfactory axons. Gap junctions involving olfactory axons were not found. However, by freeze fracture, P faces of both the axons and ensheathing cells (glia that surround the axon fascicles) contained distinctive linear arrays of particles, aligned along the small columns of extracellular space. In axons, few intramembranous particles were present outside of these arrays. Multi-helix proteins, including ion channels and connexin hemichannels, have been shown to be visible as particles by freeze fracture. This suggests that the proteins important for signal transmission are confined to the linear arrays. Such an arrangement would facilitate ephaptic transmission, calcium waves, current oscillations, and paracrine communication and may be important for olfactory neural code processing.Keywords freeze fracture; ultrastructure; olfactory bulb; ephaptic; connexins; hemichannels Olfactory receptor neurons project from the olfactory epithelium to the olfactory bulb by dense bundles of thin, unmyelinated olfactory axons (Marin-Padilla and Amieva, 1989;Daston et al., 1990;Mori, 1993). The high packing density of these axons and the absence of intervening glia suggest that olfactory coding may be affected by axoaxonal interactions.We recently demonstrated (Bokil et al., 2001) that neighboring axons are able to influence each other by ephaptic interactions-current spread through the small extracellular space. We have argued (Bokil et al., 2001) that ephaptic interactions, as well as interneuronal interactions mediated by extruded potassium ions (Bliss and Rosenberg, 1979) First, olfactory receptors of mature mammals are constantly regenerated (Graziadei and Graziadei, 1979;Graziadei and Monti Graziadei, 1983), and developing neurons of the central nervous system are often extensively coupled by gap junctions (reviewed in Kandler and Katz, 1995;Naus and Bani-Yaghoub, 1998;Chang and Balice-Gordon, 2000). Second, olfactory receptor neurons express connexins, the proteins that form gap junctions. Olfactory receptor neurons express mRNA for connexins 43 (Zhang et al., 2000), 45 (Zhang andRestrepo, 2002), and 36 (Zhang andRestrepo, 2003). Furthermore, in immun...

show abstract

Section: Discussionmentioning

confidence: 94%

Intercellular interactions in the mammalian olfactory nerve

Blinder

Pumplin

Paul

et al. 2003

J of Comparative Neurology

View full text Add to dashboard Cite

show abstract

“…Coupling of cells expressing dissimilar connexins that form hemichannels of different gating polarities is one way to establish rectifying junctions (Barrio et al, 1991;Bennett and Verselis, 1992;Verselis et al, 1994), and in some cases asymmetry can be strongly modulated by small changes in difference of holding potentials (Bukauskas et al, 2002). Interestingly, connexin35 (O'Brien et al, 1998), the fish ortholog of the neuron-specific mammalian gap junction forming protein connexin36 (Condorelli et al, 1998), has been reported to be abundantly present at both sides in the gap junction plaques between club endings and the M-cell, suggesting that electrical transmission is mediated via homotypic gap junction channels (Pereda et al, 2003a). Although the presence of additional neuronal connexins cannot be ruled out, the nonlinear behavior of these junctions suggests that hemichannels of identical connexin composition could exhibit subtle functional differences on each side of the junction, as a result, for example, of posttranslational modifications.…”

Section: Possible Contribution Of the Junctional Membranementioning

confidence: 99%

Voltage-Dependent Enhancement of Electrical Coupling by a Subthreshold Sodium Current

Curti¹,

Pereda²

2004

J. Neurosci.

View full text Add to dashboard Cite

“…The identity of several connexins that form retinal gap junctions has been elucidated in the last decade. Connexin 35/36 (O'Brien et al, 1996;Condorelli et al, 1998;O'Brien et al, 1998) was the first neuron-specific connexin identified. It has been found in a large number of neurons in the retina and central nervous system.…”

Section: Introductionmentioning

confidence: 99%

Connexin 35/36 is phosphorylated at regulatory sites in the retina

Kothmann

Li²,

Burr

et al. 2007

Vis Neurosci

View full text Add to dashboard Cite

Connexin 35/36 is the most widespread neuronal gap junction protein in the retina and central nervous system. Electrical and/or tracer coupling in a number of neuronal circuits that express this connexin are regulated by light adaptation. In many cases the regulation of coupling depends on signaling pathways that activate protein kinases such as PKA, and Cx35 has been shown to be regulated by PKA phosphorylation in cell culture systems. To examine whether phosphorylation might regulate Cx35/36 in the retina we developed phospho-specific polyclonal antibodies against the two regulatory phosphorylation sites of Cx35 and examined the phosphorylation state of this connexin in the retina. Western blot analysis with hybrid bass retinal membrane preparations showed Cx35 to be phosphorylated at both the Ser110 and Ser276 sites, and this labeling was eliminated by alkaline phosphatase digestion. The homologous sites of mouse and rabbit Cx36 were also phosphorylated in retinal membrane preparations. Quantitative confocal immunofluorescence analysis showed gap junctions identified with a monoclonal anti-Cx35 antibody to have variable levels of phosphorylation at both the Ser110 and Ser276 sites. Unusual gap junctions that could be identified by their large size (up to 32 μm 2 ) and location in the IPL showed a prominent shift in phosphorylation state from heavily phosphorylated in nighttime, dark-adapted retina to weakly phosphorylated in daytime, light-adapted retina. Both Ser110 and Ser276 sites showed significant changes in this manner. Under both lighting conditions other gap junctions varied from non-phosphorylated to heavily phosphorylated. We predict that changes in the phosphorylation states of these sites correlate with changes in the degree of coupling through Cx35/36 gap junctions. This leads to the conclusion that connexin phosphorylation mediates changes in coupling in some retinal networks. However, these changes are not global and likely occur in a cell type-specific or possibly a gap junction-specific manner.

show abstract

Cloning of a new gap junction gene (Cx36) highly expressed in mammalian brain neurons

Cited by 434 publications

References 23 publications

Intercellular interactions in the mammalian olfactory nerve

Intercellular interactions in the mammalian olfactory nerve

Voltage-Dependent Enhancement of Electrical Coupling by a Subthreshold Sodium Current

Connexin 35/36 is phosphorylated at regulatory sites in the retina

Contact Info

Product

Resources

About