Abstract
Members of the ubiquitously expressed CLC protein family of chloride channels and transporters play important roles in regulating cellular chloride and pH. The CLCs that function as Cl−/H+ antiporters, ClCs 3–7, are essential in particular for the acidification of endosomal compartments and protein degradation. These proteins are broadly expressed in the nervous system, and mutations that disrupt their expression are responsible for several human genetic diseases. Furthermore, knock-out of ClC3 and ClC7 in the mouse result in the degeneration of the hippocampus and the retina. Despite this evidence of their importance in retinal function, the expression patterns of different CLC transporters in different retinal cell types are as yet undescribed. Previous work in our lab has shown that in chicken amacrine cells, internal Cl− can be dynamic. To determine whether CLCs have the potential to participate, we used PCR and immunohistochemical techniques to examine CLC transporter expression in the chicken retina. We observed a high level of variation in the retinal expression levels and patterns among the different CLC proteins examined. These findings, which represent the first systematic investigation of CLC transporter expression in the retina, support diverse functions for the different CLCs in this tissue.
Highlights
The distribution of Cl2 across the plasma membrane is known to be tightly regulated, primarily by the activity of two Cl2 cotransport proteins: the potassium/chloride co-transporter (KCC)and the sodium/potassium/chloride co-transporter (NKCC)
A previous investigation by our group revealed that nitric oxide (NO) induces a transient elevation of cytosolic Cl2 in cultured chick amacrine cells and that this increase is due to Cl2 release from an internal compartment and not from Cl2 crossing the plasma membrane [24]
CLC antibodies raised against mammalian targets label chicken CLC proteins To examine CLC expression in the chicken retina, commercially-available antibodies raised against mammalian ClCs 3–7 were obtained
Summary
These transport proteins are known to play a critical role in setting the equilibrium potential for Cl2 by adjusting cytosolic Cl2 concentrations and determining the sign (inhibitory or excitatory) of synaptic transmission mediated by GABA- or glycine-gated Cl2 channels. Another group of Cl2 transporters, the CLC transporters, move Cl2 across cellular membranes. A subset of these transporters (ClCs 3–7) are expressed on intracellular membranes (for review, see [1]) The activity of these transporters has the potential to affect Cl2 distribution and may prove to be another important factor contributing to the dynamic nature of cytosolic Cl2 concentration [2]. CLCs are thought to operate as dimers with both homo- and heterodimers observed in expression systems [9,10]
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