Disease relevance of CLC1

• To assess the function of CLCs in plants, we searched for CLC insertion mutants in a library of Arabidopsis lines transformed by Agrobacterium tumefaciens transferred DNA (T-DNA) [1].

High impact information on CLC1

• Clathrin light chain subunits (LCa and LCb) contribute to regulation of coated vesicle formation to sort proteins during receptor-mediated endocytosis and organelle biogenesis [2].
• Disruption of the yeast gene (CLC1) leads to a slow-growth phenotype similar to that seen in strains that lack clathrin heavy chain [3].
• These properties suggest that clathrin light chain serves an important role in cell growth that can be compensated in light chain deficient cells [3].
• The yeast CLC chloride channel functions in cation homeostasis [4].
• Novel function of clathrin light chain in promoting endocytic vesicle formation [5].

Biological context of CLC1

• Overexpression of CLC1 in viable chc1-delta scd1-v strains rescued some but not all of the phenotypes displayed by these cells [6].
• As with deletion of CHC1, deletion of CLC1 results in defects in growth, receptor-mediated endocytosis, and maturation of the mating pheromone alpha-factor [7].
• The role of clathrin light chain phosphorylation in regulating clathrin function has been examined in Saccharomyces cerevisiae [8].
• Clc1p was phosphorylated in growing cells and also hyperphosphorylated upon activation of the mating response signal transduction pathway [8].
• Mutagenesis of Clc1p was used to map major phosphorylation sites to serines 52 and 112, but conversion of all 14 serines in Clc1p to alanines [S(all)A] was necessary to eliminate phosphorylation [8].

Anatomical context of CLC1

• CLC chloride channels are a family of channel proteins mediating chloride transport across the plasma membrane and intracellular membranes [9].
• However, clathrin light chain knockouts showed a decreased association of clathrin with intracellular membranes [10].
• Injection of OmCLC-3 and OmCLC-5 cRNAs into Xenopus oocytes did not elicit chloride currents, but these clones did functionally complement the gef1 phenotype of YPH250(gef), a yeast strain in which a single CLC channel (GEF1) has been disrupted by homologous recombination [11].

Physical interactions of CLC1

• Cells expressing the S(all)A mutant Clc1p displayed no defects in Clc1p binding to clathrin heavy chain, clathrin trimer stability, sorting of a soluble vacuolar protein, or receptor-mediated endocytosis of mating pheromone [8].

Other interactions of CLC1

• The yeast CLC chloride channel is proteolytically processed by the furin-like protease Kex2p in the first extracellular loop [9].
• Mating pheromone-stimulated hyperphosphorylation of Clc1p was dependent on the mating response signal transduction pathway MAP kinase Fus3p [8].
• The single yeast CLC protein Gef1p is localized to the Golgi and endosomal system [9].

Analytical, diagnostic and therapeutic context of CLC1

• The structure and physiologic role of clathrin light chain has been explored by purification of the protein from Saccharomyces cerevisiae, molecular cloning of the gene, and disruption of the chromosomal locus [3].
• The phosphorylation state of yeast clathrin light chain (Clc1p) in vivo was monitored by [32P]phosphate labeling and immunoprecipitation [8].

References