[
1980]
Nematodes have long been recognized to have peripherally located sense organs. These comprise modifications of the cuticle as papillae, pores, or setae associated with an underlying nerve process. However, their generally small size precluded any in-depth understanding of either structure or function. As recently as 1971 a review of nematode anatomy considered the nature and function of nematode sense organs within only three and a half pages. Only 5 years later, McLaren required 70 pages to review the same subject, primarily because of the recent contributions from electron microscopic studies. Although most of these studies were of animal parasites, similar studies of plant-parasitic species followed quickly, and in 1975 two major papers were published dealing with the free-living microbial feeder, Caenorhabditis elegans. This nematode has been extensively studied as a model system to investigate developmental processes, and, since it is small, it has been feasible to reconstruct with great accuracy the total cellular composition of various parts of its anatomy. These studies in turn allow us to reappraise others, especially those of the larger animal parasites where cell identities are often harder to trace. They have also shown that nerves are associated with internal tissues of the body in manners suggesting that they may monitor internal functions or detect external stimuli capable of penetrating body tissues. It therefore seems important to recognize two classes of sensory organs (1) cuticular or peripheral sense organs, and (2) internal sensory
[
Physiol Rev,
2018]
CLC anion transporters are found in all phyla and form a gene family of eight members in mammals. Two CLC proteins, each of which completely contains an ion translocation parthway, assemble to homo- or heteromeric dimers that sometimes require accessory -subunits for function. CLC proteins come in two flavors: anion channels and anion/proton exchangers. Structures of these two CLC protein classes are surprisingly similar. Extensive structure-function analysis identified residues involved in ion permeation, anion-proton coupling and gating and led to attractive biophysical models. In mammals, ClC-1, -2, -Ka/-Kb are plasma membrane Cl<sup>-</sup> channels, whereas ClC-3 through ClC-7 are 2Cl<sup>-</sup>/H<sup>+</sup>-exchangers in endolysosomal membranes. Biological roles of CLCs were mostly studied in mammals, but also in plants and model organisms like yeast and Caenorhabditis elegans. CLC Cl<sup>-</sup> channels have roles in the control of electrical excitability, extra- and intracellular ion homeostasis, and transepithelial transport, whereas anion/proton exchangers influence vesicular ion composition and impinge on endocytosis and lysosomal function. The surprisingly diverse roles of CLCs are highlighted by human and mouse disorders elicited by mutations in their genes. These pathologies include neurodegeneration, leukodystrophy, mental retardation, deafness, blindness, myotonia, hyperaldosteronism, renal salt loss, proteinuria, kidney stones, male infertility, and osteopetrosis. In this review, emphasis is laid on biophysical structure-function analysis and on the cell biological and organismal roles of mammalian CLCs and their role in disease.