A History of Gap Junction Structure: Hexagonal Arrays to Atomic Resolution

Grosely, Rosslyn; Sorgen, Paul L.

doi:10.3109/15419061.2013.775256

Cited by 10 publications

(10 citation statements)

References 67 publications

(100 reference statements)

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“…Historically, Farquhar and Palade (19) observed EMs of various epithelial cells and provided the identification of the zonula occludens (tight junction), zonula adherens (intermediary junction), and the macula adherens (desmosome). Gap junction was not delineated from tight junction until the work of Revel and Karnovsky (20), since extracellular or intermembrane gap is quite similar in tight and gap junctions (21). In later study, the treatment of samples with uranyl acetate instead of lanthanum established the presence of a 1.8-nm gap between the outer leaflets of the apposed membranes of gap junction (21).…”

Section: Discussionmentioning

confidence: 99%

“…Gap junction was not delineated from tight junction until the work of Revel and Karnovsky (20), since extracellular or intermembrane gap is quite similar in tight and gap junctions (21). In later study, the treatment of samples with uranyl acetate instead of lanthanum established the presence of a 1.8-nm gap between the outer leaflets of the apposed membranes of gap junction (21). Although the presence of functional gap junction in adipocytes has been proved in previous studies, the morphological investigations by EM in adipose tissues have not been published.…”

Section: Discussionmentioning

confidence: 99%

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Antiobesity Action of ACAM by Modulating the Dynamics of Cell Adhesion and Actin Polymerization in Adipocytes

et al. 2016

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Coxsackie virus and adenovirus receptor-like membrane protein (CLMP) was identified as the tight junctionassociated transmembrane protein of epithelial cells with homophilic binding activities. CLMP is also recognized as adipocyte adhesion molecule (ACAM), and it is upregulated in mature adipocytes in rodents and humans with obesity. Here, we present that aP2 promoter-driven ACAM transgenic mice are protected from obesity and diabetes with the prominent reduction of adipose tissue mass and smaller size of adipocytes. ACAM is abundantly expressed on plasma membrane of mature adipocytes and associated with formation of phalloidin-positive polymerized form of cortical actin (F-actin). By electron microscopy, the structure of zonula adherens with an intercellular space of ∼10-20 nm was observed with strict parallelism of the adjoining cell membranes over distances of 1-20 mm, where ACAM and g-actin are abundantly expressed. The formation of zonula adherens may increase the mechanical strength, inhibit the adipocyte hypertrophy, and improve the insulin sensitivity.Quite a few adhesion molecules have been identified by molecular genetics as well as gene expression profile studies in adipocytes derived from experimental models and human studies. For instance, only cadherins were reported to be expressed in premature adipocytes. In the cell lines, such as C3H10T1/2 and 3T3-L1 cells, N-cadherin and cadherin-11 are expressed, and they are prominently suppressed by the induction of adipocyte differentiation and downregulated to very low levels after the full differentiation (1). Transgenic (Tg) expression of dominant-negative N-cadherin decreased bone formation, delayed acquisition of peak bone mass, and increased body fat (2). Although the information of adhesion molecules in adipocyte biology is limited, we identified adipocyte adhesion molecule (ACAM) from the visceral adipose tissues of OLETF (Otsuka Long-Evans Tokushima fatty) rats by PCR-based cDNA suppressive subtraction methods (3). Mouse ACAM was independently identified as adipocyte-specific protein 5 (ASP5) from 3T3-L1 cells by using signal sequence trap by a retrovirus-mediated expression screening method (4). Human ACAM had been identified as coxsackie virus and adenovirus receptor-like membrane protein (CLMP) by bioinformatics approaches, and Raschperger et al. (5) demonstrated that CLMP is a component of the tight junction of epithelial cells and colocalized with zonula occludens-1. ACAM/CLMP belongs to CTX (cortical thymocyte marker in Xenopus), and they are characterized by extracellular variable (V-type) and constant (C2-type) immunoglobulin domains, which are involved in the homophilic adhesion and aggregation of the cells. Although we reported the expression of ACAM increased in mature adipocytes in genetically obese db/db and diet-induced obesity mice, and also in adipose tissues

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Antiobesity Action of ACAM by Modulating the Dynamics of Cell Adhesion and Actin Polymerization in Adipocytes

et al. 2016

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“…This complexity is thought to allow cells to fine-tune the conductance of chemical information, and support coupling across different cell types7. However, our understanding of the physical basis for connexin isoform compatibility, conductance, substrate selectivity and channel gating remains limited8,9, as high-resolution structural information obtained by crystallographic analysis has so far been restricted to just a single model system, connexin-26 (Cx26)10,11.…”

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confidence: 99%

Structure of native lens connexin 46/50 intercellular channels by cryo-EM

Myers

Haddad

O'neill

et al. 2018

Nature

125

187

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Gap junctions establish direct pathways for cell-to-cell communication, through the assembly of twelve subunits (connexins) that form intercellular channels connecting neighboring cells. Co-assembly of different connexin isoforms produces channels with unique properties, and enables communication across cell-types. To gain access into the structural underpinnings of connexin co-assembly, we used single particle CryoEM to determine the structure of native lens gap junction channels, composed of connexin-46 and connexin-50 (Cx46/50). We provide the first comparative analysis to connexin-26 (Cx26), which together with computational studies elucidates key energetic features governing gap junction perm-selectivity. Cx46/50 adopts an open-state conformation that is unique from the Cx26 crystal structure, yet appears to be stabilized by a conserved set of hydrophobic anchoring residues. ‘Hot spots’ of genetic mutations linked to hereditary cataract formation map to the core structural-functional elements identified in Cx46/50, rationalizing many of the disease-causing effects.

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“…It is noteworthy that several cell types can express more than one type of connexin simultaneously [73,77]. Connexins isoforms possess very similar and conserved structures, consisting of two extracellular loops, four transmembrane domains, one cytoplasmic loop, the C-terminus and the N-terminus [78]. When six units of identical connexins assemble, the resulting connexon is termed homomeric, whereas a connexon formed of different types of connexins is named heteromeric.…”

Section: Connexinsmentioning

confidence: 99%

The Role of Purinergic Signaling in the Pathophysiology of Perinatal Hypoxic-Ischemic Encephalopathy

Morais-Lima¹,

Vicentini²,

Alberto³

et al. 2020

Receptors P1 and P2 as Targets for Drug Therapy in Humans

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Perinatal hypoxic-ischemic encephalopathy (HIE), known as birth asphyxia, remains a major contributor to poor neurodevelopmental outcomes including cerebral palsy and seizures. One striking feature of HIE injury is a delayed progression of neuronal degeneration that spreads over time from the most severely damaged areas outward into neighboring undamaged regions. There is increasing evidence that these lesions act as sites of origin for waves of spreading depression (SD), a wave of neuronal and glial depolarization, that progressively enlarge the brain lesions. While the pathophysiology of SD is still under debate, there is increasing evidence that purinergic receptors in conjunction with connexin and pannexin 1 channels are necessary for sustained propagation of the waves and neuroinflammation. This review intends to discuss the relative contribution of purinergic signaling and connexin and pannexin 1 channels to trigger and spread SD waves leading to the development of progressive brain lesions under conditions of perinatal HIE.

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A History of Gap Junction Structure: Hexagonal Arrays to Atomic Resolution

Cited by 10 publications

References 67 publications

Antiobesity Action of ACAM by Modulating the Dynamics of Cell Adhesion and Actin Polymerization in Adipocytes

Antiobesity Action of ACAM by Modulating the Dynamics of Cell Adhesion and Actin Polymerization in Adipocytes

Structure of native lens connexin 46/50 intercellular channels by cryo-EM

The Role of Purinergic Signaling in the Pathophysiology of Perinatal Hypoxic-Ischemic Encephalopathy

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