Neuronal ClC-3 Splice Variants Differ in Subcellular Localizations, but Mediate Identical Transport Functions

Abstract

Background: Alternative splicing can result in proteins with distinct subcellular distributions and functions. Results: Three ClC-3 splice variants are expressed in the mammalian brain with different subcellular localizations, but identical transport properties. Conclusion: Differences in the subcellular localization of ClC-3 splice variants suggest diverse cellular functions. Significance: The existence of multiple splice variants needs to be considered when studying cellular functions of ClC-3.

Metabolic Energy Sensing by Mammalian CLC Anion/Proton Exchangers

“…We transfected HEK293T cells and used whole-cell electrophysiology to investigate the functional effects of adenine nucleotides on three CLC anion/proton exchanger isoforms, the human ClC-4 and ClC-5, and the membrane-localized mouse ClC-3 splice variant ClC-3c [16]. The expression resulted in large macroscopic currents with the specific biophysical properties of the corresponding isoforms (Figure 1B) [17].…”

Transcriptional repression of human epidermal growth factor receptor 2 by ClC‐3 Cl−/H+ transporter inhibition in human breast cancer cells

“…In heterologous mammalian expression system, ClC‐3a and ClC‐3b localized to the late endosomal/lysosomal system, whereas ClC‐3c was found in recycling endosome and plasma membrane. Depolarization‐induced outward currents were in ClC‐3c‐expressed HEK293 cells alone . In order to visualize intracellular ClC‐3 protein localization using laser scanning confocal microscopy, the immunocytochemical staining of ClC‐3 in MDA‐MB‐453 cells was carried out with an anti‐ClC‐3 antibody and Alexa Fluor 488 anti‐rabbit IgG antibody.…”

“…Depolarization-induced outward currents were in ClC-3c-expressed HEK293 cells alone. 12 In order to visualize intracellular ClC-3 protein localization using laser scanning confocal microscopy, the immunocytochemical staining of ClC-3 in MDA-MB-…”

“…A recent study by Valdivieso et al showed a role for Cl − channels as transcriptional regulators that control the expression of specific genes. ClC‐3 proteins localize in intracellular organelles and function as Cl − /H + transporters . ClC‐3 also contributes to osteo‐differentiation, and its overexpression has been shown to enhance the gene expression of osteogenic markers such as alkaline phosphatase, osteocalcin, and bone sialoprotein .…”

“…ClC-3 proteins localize in intracellular organelles and function as Cl − /H + transporters. 11,12 ClC-3 also contributes to osteodifferentiation, and its overexpression has been shown to enhance the gene expression of osteogenic markers such as alkaline phosphatase, osteocalcin, and bone sialoprotein. 13 Furthermore, inhibition of ClC-3 downregulates the expression of the matrix metalloproteinases MMP2 and MMP9 in osteosarcoma cells.…”