Is half of a lens gap junction channel better than none? Focus on "properties of two cataract-associated mutations located in the NH2 terminus of connexin 46".
نویسنده
چکیده
GAP JUNCTIONS ARE CLUSTERS of intercellular channels that allow the exchange of ions and small metabolites between adjacent cells (1). Intercellular channels form when two hemichannels, one contributed by each of the opposed cells, align in the extracellular space. Hemichannels are oligomers of six connexin proteins, and some of these also have the ability to form functioning channels in nonjunctional plasma membranes (4, 11). The overall importance of gap junction channels is highlighted by the finding that mutations in many of the human connexin genes cause a broad spectrum of hereditary diseases including lens cataract (9). The physiological role(s) of hemichannels have remained more enigmatic, although an increase in hemichannel activity has been linked to connexin mutations that cause human skin diseases like keratitis-ichthyosis-deafness (KID) syndrome (7). In this issue of American Journal of Physiology-Cell Physiology, Tong et al. (10) examine the functional properties of two connexin46 (Cx46) mutations linked to cataract and show that in addition to defects in gap junctional coupling, both mutations also had significant alterations in hemichannel activity, highlighting a possible role for Cx46 hemichannels in the normal physiology of the lens. As an avascular organ, the lens is dependent on gap junction-mediated communication for its homeostasis. The lens contains a single layer of epithelial cells spanning the anterior half of the lens surface, differentiating fiber cells that constitute the lens cortex, and mature fiber cells that make up the lens core. All of these cell types are coupled to neighboring cells by gap junctions, and Cx46 is a major component of the fiber cell channels in both the cortex and core (8). The lens depends on ion transport to create an internal circulating current, with Na being the primary current carrier (2). Na , coupled with water, enters the lens at the anterior and posterior poles and flows inward along the extracellular spaces. Within the lens, Na is
منابع مشابه
Properties of two cataract-associated mutations located in the NH2 terminus of connexin 46.
Mutations in connexin 46 are associated with congenital cataracts. The purpose of this project was to characterize cellular and functional properties of two congenital cataract-associated mutations located in the NH2 terminus of connexin 46: Cx46D3Y and Cx46L11S, which we found localized to gap junctional plaques like wild-type Cx46 in transfected HeLa cells. Dual two-microelectrode-voltage-cla...
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Connexin channels play a critical role in maintaining metabolic homeostasis and transparency of the lens. Mutations in connexin genes are linked to congenital cataracts in humans. The G143R missense mutation on connexin (Cx) 46 was recently reported to be associated with congenital Coppock cataracts. Here, we showed that the G143R mutation decreased Cx46 gap junctional coupling in a dominant ne...
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Eukaryotic cells possess a unique way to communicate with each other by passing metabolites and small molecules through protein pores that connect adjacent cells. Although there are many types and families of protein pores, connexins comprise a unique family. Six connexin monomers assemble into a hemichannel, which is transported to the cell membrane. An opposing cell membrane containing compat...
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ورودعنوان ژورنال:
- American journal of physiology. Cell physiology
دوره 304 9 شماره
صفحات -
تاریخ انتشار 2013