Functional reconstitution of a chloride channel bares its soul
| Autor: | H. Criss Hartzell, Chelsey Chandler Ruppersburg |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
In Vitro Techniques Spodoptera Biology Neuronal signaling Calmodulin Chloride Channels Commentaries Internal medicine Sf9 Cells medicine Limited sampling Animals Humans Secretion Receptor Anoctamin-1 Multidisciplinary Biological Transport Transporter Sequence Analysis DNA Neoplasm Proteins Cell biology Endocrinology Mutagenesis Chromatography Gel Chloride channel Efflux Ion Channel Gating Intracellular Plasmids |
| Zdroj: | Proceedings of the National Academy of Sciences. 110:19185-19186 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.1319415110 |
| Popis: | Chloride channels have been called the poor cousins of the aristocratic cation channels because their physiological functions involve “cleaning up the mess after the party” (1). Although Cl− channels are not as glamorous as the Na+, Ca2+, and K+ channels dominating neuronal signaling, their functions are indispensable (2), as exemplified by cholera caused by superactivation of a Cl− channel (CFTR) in the gut and cystic fibrosis caused by insufficiency of the same Cl− channel in the lung. In part, our understanding of these navels of negativity has been slow to ripen because the molecular zoo of Cl− channels is incomplete. Humans have >200 cation channel genes in >20 families, but only four Cl− channel families comprised of a paltry 34 genes were known until recently. This limited sampling has restricted efforts to uncover the essence of Cl− channel pores. Therefore, a sensation occurred when the Cl− channel gene superfamily blossomed in size in 2008 with the addition of a 10-gene family called TMEM16 , also called Anoctamin (3⇓–5). TMEM16A and TMEM16B encode subunits of Ca2+-activated Cl− channels (CaCCs) that are widely expressed throughout the body. CaCCs open when intracellular Ca2+ rises, for example following activation of G protein-coupled receptors by certain hormones. CaCCs’ best known function is in epithelial fluid secretion, a role played in parallel with CFTR (Fig. 1). The aqueous portion of secretions such as tears, saliva, milk, and pancreatic juice is produced by cells that actively accumulate Cl− from their blood-side by pumps and transporters, and then release Cl− into the glandular ducts through Cl− channels on the other side of the cell. Cl− efflux drives fluid secretion as Na+ and water follow … [↵][1]1To whom correspondence should be addressed. E-mail: criss.hartzell{at}emory.edu. [1]: #xref-corresp-1-1 |
| Databáze: | OpenAIRE |
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