Connexin46, a novel lens gap junction protein, induces voltage-gated currents in nonjunctional plasma membrane of Xenopus oocytes.

Paul, David L.; Ebihara, Lisa; Takemoto, L.; Swenson, Kirsten G.; Goodenough, Daniel A.

doi:10.1083/jcb.115.4.1077

Cited by 558 publications

(440 citation statements)

References 49 publications

(69 reference statements)

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“…RT-PCR products of the appropriate size for all three connexins were amplified from the lens RNA, but only Cx43 was amplified from the liver RNA. This result is consistent with previous observations from mammals and birds that the Cx46 and Cx50 subfamilies are predominantly expressed in the lens (Paul et al, 1991;White et al, 1992;Rup et al, 1993;Jiang et al, 1994), whereas Cx43 is expressed in a variety of tissues, including the vascular system . RT-PCR analysis of adult lens RNA with primers specific for Cx43.4 (Essner et al, 1996), Cx35 (McLachlan et al, 2003, and Cx45.6 (Christie et al, manuscript in preparation) failed to detect expression (data not shown).…”

Section: Mouse and Chickensupporting

confidence: 93%

“…The expression of three different connexins has been detected in the mammalian lens. Cx46 and Cx50 are mainly expressed in the lens fiber cells (Paul et al, 1991;White et al, 1992), whereas Cx43 is restricted to the anterior lens epithelium (Yancey et al, 1992). The chicken orthologues of these connexins have been identified as Cx56, Cx45.6, and Cx43 (Musil et al, 1990;Rup et al, 1993;Jiang et al, 1994).…”

Section: Introductionmentioning

confidence: 99%

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Expression of connexin48.5, connexin44.1, and connexin43 during zebrafish (Danio rerio) lens development

Cheng

Christie

Valdimarsson

2003

Developmental Dynamics

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Connexins (Cx), the protein units of gap junctions, play important roles in lens development and homeostasis. Here, we report the mRNA expression patterns of zebrafish Cx48.5, Cx44.1, Cx43 during lens development. The expression of all three connexins in the adult lens was first confirmed by reverse transcriptase-polymerase chain reaction. By whole-mount in situ hybridization, we detected Cx48.5 expression throughout the lens, except the lateral lens epithelium, at 36 hours postfertilization (hpf). The pattern remained the same at 2 days postfertilization (dpf). By 3 and 4 dpf, Cx48.5 expression was restricted to the differentiating lens fibers in the equatorial and medial regions. Cx44.1 was expressed in a similar manner as Cx48.5 from 36 hpf to 4 dpf. However, Cx44.1 expression was also detected in the lens at 24 hpf. Cx43 expression was detected throughout the lens at 24 and 36 hpf but became restricted to the lateral epithelium at later stages. Developmental Dynamics 228:709 -715, 2003.

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Section: Mouse and Chickensupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Expression of connexin48.5, connexin44.1, and connexin43 during zebrafish (Danio rerio) lens development

Cheng

Christie

Valdimarsson

2003

Developmental Dynamics

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“…Cx46 was obtained from Dr. D. Paul [3]. Cx32E 1 43 [4] in the vector pGEM3Z (Pomega) was cut with BamHI and PmlI.…”

Section: Methodsmentioning

confidence: 99%

Exchange of conductance and gating properties between gap junction hemichannels

Dahl

1999

FEBS Letters

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Gap junction channels span the membranes of two adjacent cells and allow the gated transit of molecules as large as second messengers from cell to cell. The structure of the gap junction channel pore is not resolved. For identification of pore determinants we used a chimera of two connexins, cx46 and cx32E 1 43, that form membrane channels with distinct unit conductances and channel kinetics. Exchange of the first transmembrane segment (M1) between these connexins resulted in a chimera that exhibited most of the channel properties of the M 1 donor, including single channel conductance, channel kinetics, and the preference to dwell at a subconductance level. The M 1 segment thus appears to be an important determinant of conductance and gating properties of connexin channels.z 1999 Federation of European Biochemical Societies.

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“…Thus, there was no change in the current flowing into the extracellular space, and the hemichannels were closed before opening to form a cell-cell channel. When expression of Cx46 in Xenopus oocytes was found to be fatal and to cause a large non-specific increase in membrane conductance in low Ca 2+ conditions, it seemed to be a rule that proved the exception: opening of (non-junctional) hemichannels is bad for cells, and something unusual about Cx46 expressed in oocytes allows hemichannel opening unless relatively high Ca 2+ concentrations are added to prevent it [8,9]. …”

mentioning

confidence: 99%

New roles for astrocytes: Gap junction hemichannels have something to communicate

Bennett

Contreras

Bukauskas

et al. 2003

Trends in Neurosciences

376

279

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Gap junctions are clusters of aqueous channels that connect the cytoplasm of adjoining cells. Each cell contributes a hemichannel, or connexon, to each cell-cell channel. The cell-cell channels are permeable to relatively large molecules, and it was thought that opening of hemichannels to the extracellular space would kill cells through loss of metabolites, collapse of ionic gradients and influx of Ca 2+ . Recent findings indicate that specific non-junctional hemichannels do open under both physiological and pathological conditions, and that opening is functional or deleterious depending on the situation. Most of these studies utilized cells in tissue culture that expressed a specific gap junction protein, connexin 43. Several such examples are reviewed here, with a particular focus on astrocytes.Gap junctions mediate intercellular communication by providing ultrastructural cytoplasmic continuity, and they are integral to formation of the functional syncytium of astrocytes. Each of the joined cells contributes a hemichannel or connexon to each cell-cell channel ( Figure 1; Box 1). Each hemichannel comprises a hexamer of connexins arranged around a central pore, and the cell-cell channels are gated by several stimuli, including transjunctional voltage, low pH and various pharmacological agents. Connexins are encoded by a gene family with at least 20 members in mammals [1].Gap-junction pores are nominally 1.0-1.5 nm in diameter and are permeable to molecules of 1 kDa [2]. Junctions formed from connexin 43 (Cx43), the predominant connexin in astrocytes, are permeable to Lucifer Yellow (443 Da, −2 charge) and propidium (420 Da, +2 charge). Other connexins appear to be more charge selective: Cx32 is more permeable to anions and Cx45 is more permeable to cations [2]. Single-channel conductance varies widely, from ~15 pS for Cx36 [3] and 110 pS for Cx43 [4] to ~375 pS for Cx37 [5]. The maximum size of permeant species also varies. Such diversity in selectivity and conductance are likely to account for the expansion of the connexin family. Why shouldn't hemichannels be open?Given the permeability and conductance of gap junctions, and the expectation that an open hemichannel would have twice the conductance and permeability of a cell-cell channel (in terms of ion or molecular flux, rather than selectivity), it was thought unlikely that hemichannels in the non-junctional membrane would open [6]. Direct evidence for this was provided by measurements during formation of the first channel between a newly apposed pair of cells. Each cell was held at a different potential, and then when the first channel NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript opened, increased current was seen in the cell held at a more positive potential and decreased (more negative) current was seen in the other cell, but the sum of the currents clamping the two cells remained constant [7]. Thus, there was no change in the current flowing into the extracellular space, and the hemichannels were closed before openin...

show abstract

Connexin46, a novel lens gap junction protein, induces voltage-gated currents in nonjunctional plasma membrane of Xenopus oocytes.

Cited by 558 publications

References 49 publications

Expression of connexin48.5, connexin44.1, and connexin43 during zebrafish (Danio rerio) lens development

Expression of connexin48.5, connexin44.1, and connexin43 during zebrafish (Danio rerio) lens development

Exchange of conductance and gating properties between gap junction hemichannels

New roles for astrocytes: Gap junction hemichannels have something to communicate

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