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Lymphatic Connexins and Pannexins in Health and Disease.

This review highlights current knowledge on the expression and function of connexins and pannexins, transmembrane channel proteins that play an important role in intercellular communication, in both the developing and mature lymphatic vasculature. A particular focus is given to the involvement of these proteins in functions of the healthy lymphatic system. We describe their influence on the maintenance of extracellular fluid homeostasis, immune cell trafficking to draining lymph nodes and dietary nutrient absorption by intestinal villi. Moreover, new insights into connexin mutations in primary…

Impact of Astroglial Connexins on Modafinil Pharmacological Properties.

STUDY OBJECTIVES: Modafinil is a non-amphetaminic wake-promoting compound used as therapy against sleepiness and narcolepsy. Its mode of action is complex, but modafinil has been recently proposed to act as a cellular-coupling enhancer in glial cells, through modulation of gap junctions constituted by connexins. The present study investigated in mice the impact of connexins on the effects of modafinil using connexin inhibitors. METHODS: Modafinil was administered alone or combined with inhibitors of astrocyte connexin, meclofenamic acid, or flecainide, respectively, acting on Cx30 and Cx43. S…

Roles of connexins in testis development and spermatogenesis.

The development and differentiation of cells involved in spermatogenesis requires highly regulated and coordinated interactions between cells. Intercellular communication, particularly via connexin43 (Cx43) gap junctions, plays a critical role in the development of germ cells during fetal development and during spermatogenesis in the adult. Loss of Cx43 in the fetus results in a decreased number of germ cells, while the loss of Cx43 in the adult Sertoli cells results in complete inhibition of spermatogenesis. Connexins 26, 32, 33, 36, 45, 46 and 50 have also been localized to specific compartm…

Connexins form functional hemichannels in porcine ciliary epithelium.

The expression of connexins in the ciliary epithelium is consistent with gap junctions between the pigmented (PE) and nonpigmented ciliary epithelium (NPE) that form when connexon hemichannels from adjacent cells pair to form a channel. Here we present evidence that suggests undocked connexons may form functional hemichannels that permit exchange of substances between NPE and the aqueous humor. Intact porcine eyes were perfused via the ciliary artery and propidium iodide (PI) (MW 668) was added to the aqueous humor compartment as a tracer. After calcium-free solution containing PI was introduc…

Distinctive actions of connexin 46 and connexin 50 in anterior pituitary folliculostellate cells.

Folliculostellate cell gap junctions establish a network for the transmission of information within the anterior pituitary. Connexins make up gap junction channels. Changes in connexin (Cx) turnover modify gap junction-mediated intercellular communication. We have reported that cytokines and hormones influence Cx43 turnover and coupling in folliculostellate cells and in the folliculostellate cell line TtT/GF. In addition, the expression of different connexins alters intercellular communication and connexins may have functions besides cell coupling. Here we assessed the expression, turnover and…

Connexins in melanoma: Potential role of Cx46 in its aggressiveness.

Melanoma is the most aggressive skin cancer, and in metastatic advanced states, it is completely refractory to chemotherapy. Therefore, it is relevant to understand the molecular bases that rule their aggressiveness. Connexins (Cxs) are proteins that under normal physiological conditions participate in intercellular communication, via the exchange of signaling molecules between the cytoplasm and extracellular milieu and the exchange of ions/second messengers between the cytoplasm of contacting cells. These proteins have shown important roles in cancer progression, chemo- and radiotherapy resis…

Aberrant expression pattern of gap junction connexins in endometriotic tissues.

The expression of gap junction connexins (Cx) in the female reproductive tract of rodents and in the human endometrium is highly regulated by steroid hormones. Here we have investigated the distribution and regulation properties of Cx43, Cx26 and Cx32 in the human ectopic endometrium of 41 patients, using immunohistochemistry. The biopsies were obtained during the early or late follicular phase (26 cases), during the corpus luteum phase (five cases) and after a 6 month treatment with a gonadotrophin-releasing hormone (GnRH) agonist (three cases) or progestin (seven cases). Aberrant expression …

Role of astrocytes connexins - pannexins in acute brain injury.

Acute brain injuries (ABIs) encompass a broad spectrum of primary injuries such as ischemia, hypoxia, trauma, and hemorrhage that converge into secondary injury where some mechanisms show common determinants. In this regard, astroglial connexin and pannexin channels have been shown to play an important role. These channels are transmembrane proteins sharing similar topology and form gateways between adjacent cells named gap junctions (GJs) and pores into unopposed membranes named hemichannels (HCs). In astrocytes, GJs and HCs enable intercellular communication and have active participation in

Role of connexins in female reproductive system and endometriosis.

Gap junction form channels between the cells and facilitate the function of cellular cross talk. Connexins, the gap junction proteins play an essential role in female reproductive health and its expression anomalies are correlated with female reproductive disorders like polycystic ovarian syndrome, recurrent miscarriage, pre-term birth and endometriosis. Endometriosis is a chronic gynecologic disorder caused by ectopic endometrial lesions growing outside the uterine cavity. Embryonic implantation is adversely affected in case of endometriosis leading to infertility. Endometriosis also interfer…

Roles of connexins in atherosclerosis and ischemia-reperfusion injury.

Connexins are members of a large family of transmembrane proteins that oligomerize to form connexons or hemichannels, and connexons of adjacent cells dock to make gap junction channels. These channels allow the exchange of ions and small metabolites between the cytosol and extracellular space, or between the cytosols of neighbouring cells. Connexins are important in cardiovascular physiology; they support conducted vascular responses and allow for coordinated contraction of the heart. Four main connexins are expressed in the cardiovascular system: Cx37, Cx40, Cx43 and Cx45. Their expression pa…

Connexins participate in the initiation and progression of atherosclerosis.

Connexins are members of a large family of transmembrane proteins that form hemichannels or gap junctions. These channels allow the exchange of ions and small metabolites between the cytosol and extracellular space or between neighboring cells. Connexins are important in vascular physiology; they support radial and longitudinal cell-to-cell communication in the vascular wall. Four connexins are expressed in the vascular wall: Cx37, Cx40, Cx43, and Cx45. Their expression is not uniform in all blood vessels and varies with vascular territory and species. Significant changes in the expression pat…

Unique and shared functions of different connexins in mice.

BACKGROUND: Connexins are the protein subunits of intercellular gap junction channels. In mammals, they are encoded by a family of at least 15 genes, which show cell-type-specific but overlapping patterns of expression. Mice lacking connexin43 (Cx43) die postnatally from obstruction of the right ventricular outflow tract of the heart. To discriminate between the unique and shared functions of Cx43, Cx40 and Cx32, we generated two 'knock-in' mouse lines, Cx43KI32 and Cx43KI40, in which the coding region of the Cx43 gene was replaced, respectively, by the coding regions of Cx32 or Cx40. RESULTS…

[Connexin astrocytopathy and novel therapeutic strategy targeting connexin hemichannels in demyelinating disease].

Recently, we reported aquaporin-4 (AQP4) loss without perivascular deposition of complements or immunoglobulins in autopsied cases with multiple sclerosis (MS), neuromyelitis optica (NMO) and Baló's disease (BD). To investigate the relationship between astrocytopathy and demyelination, we examined the expression of connexins (Cx), which form gap junction channels between astrocytes and oligodendrocytes. We pathologically evaluated the expressions of astrocytic Cx43/Cx30 and oligodendroglial Cx47/Cx32 relative to those of other astrocytic and oligodendrocyte/myelin markers among the autopsied c…

Connexins in metabolic control: linking brain cellular communication to systemic homeostasis.

Connexins, a family of transmembrane proteins, are essential for intercellular communication in the mammalian central nervous system, particularly through their assembly into gap junction channels. This review explores the central role of connexin-mediated signalling in hypothalamic regulation of nutrient metabolism and energy homeostasis, together with the function of connexins in peripheral metabolic organs. Focusing on connexins Cx43 and Cx30, we discuss their specific expression within hypothalamic neuroglial populations, including astrocytes and tanycytes, and their involvement in glucose…

Кровавые экзотические коннексины и небольшие РНК были связаны с демиелинизирующими заболеваниями.

ЦЕЛИ: Оценка экзосомы крови (Ex)-коннексина (Cx)43 (кодируется GJA1) и ее усеченной изоформы при множественных склерозах (MS) и оптицическом расстройстве нейромиелита (NMOSD), которые демонстрируют явные изменения в астроглиальном Cx43. МЕТОДЫ: 48 пациентов с сером (34 пациента с релапсирующими реактивными выбросами, 14 - вторичными), 35 - с NMOSD, 20 - с другими воспалительными неврологическими заболеваниями (OIND) и 17 - с здоровыми средствами контроля (HC) были подвергнуты количественному плёту для Cx43, одномолекулярному массиву для нейрофильм-L и количественной цепной реакции полимеразы н

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… Connexins (Cxs) are transmembrane proteins that form gap junction channels. …

Understanding the Role of ATP Release through Connexins Hemichannels during Neurulation.

Neurulation is a crucial process in the formation of the central nervous system (CNS), which begins with the folding and fusion of the neural plate, leading to the generation of the neural tube and subsequent development of the brain and spinal cord. Environmental and genetic factors that interfere with the neurulation process promote neural tube defects (NTDs). Connexins (Cxs) are transmembrane proteins that form gap junctions (GJs) and hemichannels (HCs) in vertebrates, allowing cell-cell (GJ) or paracrine (HCs) communication through the release of ATP, glutamate, and NAD+; regulating proces…

Connexins in endothelial barrier function - novel therapeutic targets countering vascular hyperpermeability.

Prolonged vascular hyperpermeability is a common feature of many diseases. Vascular hyperpermeability is typically associated with changes in the expression patterns of adherens and tight junction proteins. Here, we focus on the less-appreciated contribution of gap junction proteins (connexins) to basal vascular permeability and endothelial dysfunction. First, we assess the association of connexins with endothelial barrier integrity by introducing tools used in connexin biology and relating the findings to customary readouts in vascular biology. Second, we explore potential mechanistic ties be…

Multiple roles of connexins in atherosclerosis- and restenosis-induced vascular remodelling.

Endothelial dysfunction is the initial step in atherosclerotic plaque development in large- and medium-sized arteries. This progressive dise … ndothelialization increases the risk of thrombosis. This review provides an overview of the role of connexins, a large family of transmembrane proteins, in vascular remodelling associated with atherosclerosis and restenosis. The connexins expressed in the vascular wall are Cx37, Cx40, Cx43 and Cx45; their expressions vary with vascular territory and species …

Battle of the hemichannels--Connexins and Pannexins in ischemic brain injury.

Perinatal ischemic brain injury can occur as a result of a global ischemic insult or focal ischemic stroke in the preterm or full-term neonate. One of the most striking features of HI injury is that, after initial recovery of cellular oxidative metabolism, there is a delayed, 'secondary' mitochondrial failure that spreads over time from the most severely damaged areas outwards, into previously undamaged regions. This secondary failure is accompanied by transient seizure activity and cytotoxic edema. The specific mechanisms of this spread are poorly understood, but it is at least partly associa

Connexins and pannexins: Coordinating cellular communication in the testis and epididymis.

Gap junctions and connexins are critical for coordinating cellular functions in complex epithelia. In recent years there has been increased interest in understanding the regulation and function of gap junctions in both the testis and epididymis. Studies in transgenic mice in which connexin 43 (Cx43) is mutated or is knocked down only in Sertoli cells have demonstrated the essential role of Cx43 in spermatogenesis and differentiation of Sertoli cells. In the epididymis developmental studies have shown a role for numerous connexins in the differentiation of epithelial cells and communication bet…