S100A13 and S100A6 exhibit distinct translocation pathways in endothelial cells.
S100 proteins have attracted great interest in recent years because of their cell- and tissue-specific expression and association with various human pathologies. Most S100 proteins are small acidic proteins with calcium-binding domains - the EF hands. It is thought that this group of proteins carry out their cellular functions by interacting with specific target proteins, an interaction that is mainly dependent on exposure of hydrophobic patches, which result from calcium binding. S100A13, one of the most recently identified members of the S100 family, is expressed in various tissues. Interestingly, hydrophobic exposure was not observed upon calcium binding to S100A13 even though the dimeric form displays two high- and two low- affinity sites for calcium. Here, we followed the translocation of S100A13 in response to an increase in intracellular calcium levels, as protein translocation has been implicated in assembly of signaling complexes and signaling cascades, and several other S100 proteins are involved in such events. Translocation of S100A13 was observed in endothelial cells in response to angiotensin II, and the process was dependent on the classic Golgi-ER pathway. By contrast, S100A6 translocation was found to be distinct and dependent on actin-stress fibers. These experiments suggest that different S100 proteins utilize distinct translocation pathways, which might lead them to certain subcellular compartments in order to perform their physiological tasks in the same cellular environment.
Department of Pediatrics, Division of Clinical Chemistry and Biochemistry, University of Zurich, Steinwiesstr. 75, CH-8032 Zurich, Switzerland.
Hsiao-Ling
HL
Hsieh
Beat W
BW
Schäfer
Jos A
JA
Cox
Claus W
CW
Heizmann
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D020126:Brefeldin A / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology*; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D020756:Coatomer Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D018613:Microscopy, Confocal; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology*; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000378:metabolism*; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism; D022161:Transport Vesicles / Q000187:drug effects / Q000378:metabolism
D018797:Cell Cycle Proteins; D020756:Coatomer Protein; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C511523:S100A13 protein, human; C055351:S100A6 protein, human; D000804:Angiotensin II; D020126:Brefeldin A; D002118:Calcium