Gap Junctions: Basic Structure and Function

Meşe, Gülistan; Richard, Gabriele; White, Thomas W.

doi:10.1038/sj.jid.5700770

Cited by 394 publications

(366 citation statements)

References 68 publications

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“…and small molecules (cAMP and IP 3 , etc.) (12,14). These chemical species have been implicated as second messengers and play a role in synapse formation among neocortical excitatory neurons (35).…”

Section: Discussionmentioning

confidence: 99%

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Neonatal CX26 removal impairs neocortical development and leads to elevated anxiety

Chen

Liu

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Electrical coupling between excitatory neurons in the neocortex is developmentally regulated. It is initially prominent but eliminated at later developmental stages when chemical synapses emerge. However, it remains largely unclear whether early electrical coupling networks broadly contribute to neocortical circuit formation and animal behavior. Here, we report that neonatal electrical coupling between neocortical excitatory neurons is critical for proper neuronal development, synapse formation, and animal behavior. Conditional deletion of Connexin 26 (CX26) in the superficial layer excitatory neurons of the mouse neocortex around birth significantly reduces spontaneous firing activity and the frequency and size of spontaneous network oscillations at postnatal day 5-6. Moreover, CX26-conditional knockout (CX26-cKO) neurons tend to have simpler dendritic trees and lower spine density compared with wild-type neurons. Importantly, early, but not late, postnatal deletion of CX26, decreases the frequency of miniature excitatory postsynaptic currents (mEPSCs) in both young and adult mice, whereas miniature inhibitory postsynaptic currents (mIPSCs) were unaffected. Furthermore, CX26-cKO mice exhibit increased anxiety-related behavior. These results suggest that electrical coupling between excitatory neurons at early postnatal stages is a critical step for neocortical development and function.CX26 | development | anxiety | neocortex D uring neocortical development, gap junction-mediated electrical coupling plays a critical role in various developmental processes, including neuronal migration (1, 2), synaptogenesis (3), and synchronous firing (4, 5). It is generally believed that gap junction-mediated communication between excitatory neurons during development is required for the formation of chemical synapses (6). For example, we previously showed that sister excitatory neurons in the neocortex are initially electrically coupled, and blockade of this electrotonic communication impairs the subsequent formation of specific chemical synapses between them in ontogenetic neuronal clones (7), as well as the functional similarity (8). Whereas these studies have provided crucial insights into the role of gap junctions in the precise microcircuit assembly of excitatory neurons and functional organization of the neocortex, whether electrical coupling-mediated networks contribute to the overall development of the neocortex and animal behavior remains largely unknown.Electrical coupling networks among excitatory neurons in the neocortex are developmentally regulated. Electrical couplings are the morphological correlates of dye coupling and low resistance intercellular pathways (9). Functional electrical coupling between excitatory neurons has been abundantly observed at late embryonic and early postnatal stages (10, 11). As electrical synapses approach the time point of their elimination, chemical connections between excitatory neurons begin to emerge, illustrating a sequential developmental time course for the two types of connect...

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Section: Discussionmentioning

confidence: 99%

“…The gap junction channel directly connects the cytoplasm of two neighboring cells and allows the nonselective exchange of ions and small organic molecules (12). The types of connexins in a channel can influence channel properties such as conductance and selectivity (13).…”

mentioning

confidence: 99%

Neonatal CX26 removal impairs neocortical development and leads to elevated anxiety

Chen

Liu

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…They allow the bidirectional passage of ions, metabolites and secondary messengers in a process known as gap junctional intercellular communication (GJIC) (Mese et al, 2007). GJIC has been implicated in the regulation of homeostasis and a diverse array of cellular functions related to cell specialization, growth and differentiation (Herve et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Cx43 suppresses mammary tumor metastasis to the lung in a Cx43 mutant mouse model of human disease

et al. 2010

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Gap junctions, the channels formed by the connexin (Cx) family of proteins, are responsible for direct intercellular communication. Although connexins are considered as tumor suppressors, their overall role in cancer onset, progression and metastasis is somewhat controversial. This study uses a novel Cx43 mutant mouse model (G60S mice) and cross-breeding strategies to determine the role of Cx43 in all stages of breast tumorigenesis. G60S mice were cross-bred with ErbB2 overexpressing mice, and spontaneous and 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumor development was evaluated. Mice were killed when tumors reached B1 cm 3 or when mice showed signs of critical illness. In both spontaneous and DMBA studies, onset of palpable tumors was delayed in G60S mice compared with mice in control groups. Moreover, while tumors from control mice reached the size threshold, most DMBA-exposed Cx43 mutant mice were killed prematurely because of labored breathing, independent of the presence of a palpable tumor. Reduced Cx43 levels in Cx43 mutant mice were accompanied by extensive mammary gland hyperplasia. Lung histology revealed that all Cx43 mutant mice exhibited mammaglobin-positive mammary gland metastases to the lung, and the number of metastases was increased by threefold in Cx43 mutant mice on treatment with DMBA. Thus, while reduced levels of Cx43 delayed the onset of palpable tumors, normal Cx43 levels inhibited mammary gland tumor metastasis to the lungs. Understanding the mechanisms of how Cx43, which is expressed primarily in myoepithelial cells, inhibits mammary gland tumor metastasis is critical as Cx43 is assessed as a candidate for therapeutic intervention.

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“…Direct cytoplasmic connections between cells in close physical proximity could also be formed, principally to allow the exchange of small molecules. Prominent examples of these structures are the gap junctions (Me ş e et al, 2007) in animal cells, as well as plasmodesmata in plants (Lucas et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Intercellular organelle trafficking by membranous nanotube connections: a possible new role in cellular rejuvenation?

Lim

Tang

2012

Cell Communication & Adhesion

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Cells could make actin-based fi lopodial extensions that connect up with other cells. Such close-ended, actin-based fi lopodial bridges, or cytonemes, have been observed during developmental and pathological processes. On the other hand, tunneling nanotubes (TNTs) form conduits with open ends that allow transfer of cytoplasmic materials and organelles between cells. The past years have witnessed the description of TNTs in multiple cell types, with a range of interesting physiological and pathophysiological activities. Some hints of the molecular components that drive their formations are now emerging. Recent work has further suggested that TNTs could be important in regenerative transfer of large cellular components, including organelles such as mitochondria and lysosomes between senescing and younger cell types (at least for cells in culture). These fi ndings have intriguing implications in cell biology and regenerative medicine.

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Gap Junctions: Basic Structure and Function

Cited by 394 publications

References 68 publications

Neonatal CX26 removal impairs neocortical development and leads to elevated anxiety

Neonatal CX26 removal impairs neocortical development and leads to elevated anxiety

Cx43 suppresses mammary tumor metastasis to the lung in a Cx43 mutant mouse model of human disease

Intercellular organelle trafficking by membranous nanotube connections: a possible new role in cellular rejuvenation?

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