Endocytosis function of a ligand-gated ion channel homolog in Caenorhabditis elegans.
Ligand-gated ion channels are transmembrane proteins that respond to a variety of transmitters, including acetylcholine, gamma-aminobutyric acid (GABA), glycine, and glutamate [1 and 2]. These proteins play key roles in neurotransmission and are typically found in the nervous system and at neuromuscular junctions [3]. Recently, acetylcholine receptor family members also have been found in nonneuronal cells, including macrophages [4], keratinocytes [5], bronchial epithelial cells [5], and endothelial cells of arteries [6]. The function of these channels in nonneuronal cells in mammals remains to be elucidated, though it has been shown that the acetylcholine receptor alpha7 subunit is required for acetylcholine-mediated inhibition of tumor necrosis factor release by activated macrophages [4]. We show that cup-4, a gene required for efficient endocytosis of fluids by C. elegans coelomocytes, encodes a protein that is homologous to ligand-gated ion channels, with the highest degree of similarity to nicotinic acetylcholine receptors. Worms lacking CUP-4 have reduced phosphatidylinositol 4,5-bisphosphate levels at the plasma membrane, suggesting that CUP-4 regulates endocytosis through modulation of phospholipase C activity.
Patton
Andrea
A
Department of Molecular and Cellular Biology, Life Sciences South, Room 531, University of Arizona, Tucson, Arizona 85721, USA.
Knuth
Sarah
S
Schaheen
Basil
B
Dang
Hope
H
Greenwald
Iva
I
Fares
Hanna
H
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000502:physiology*; D017931:DNA Primers; D018076:DNA, Complementary / Q000235:genetics; D004705:Endocytosis / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins; D007473:Ion Channels / Q000235:genetics / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D010738:Type C Phospholipases / Q000378:metabolism
C504071:CUP-4 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D018076:DNA, Complementary; D007473:Ion Channels; D019269:Phosphatidylinositol 4,5-Diphosphate; D011978:Receptors, Nicotinic; D049452:Green Fluorescent Proteins; D010738:Type C Phospholipases