Conditions associated with ER dysfunction activate homer 1a expression.
Homer proteins physically link metabotropic glutamate receptors with IP3 receptors located at the endoplasmic reticulum (ER) and thereby modulate receptor-activated calcium signaling. Homer 1a, the short form of constitutively expressed homer 1 proteins, exerts dominant negative activity with respect to homer 1 proteins by interfering with the formation of multiprotein complexes. Homer 1a is an immediate early gene, the expression of which is activated by various stimuli including glutamate receptor activation. The mechanisms underlying activation of homer 1a expression are however, not fully understood. Here, we show that homer 1a expression is induced in neuronal cell cultures under experimental conditions associated with ER dysfunction. Increased homer 1a mRNA levels were found in 2 sets of cultures: in those exposed to thapsigargin, a specific inhibitor of ER Ca2+-ATPase, after a transient depletion of ER calcium stores through exposure to calcium-free medium supplemented with EGTA, and in those exposed to a proteasome inhibitor known to induce ER dysfunction. Thus, homer 1a expression may be activated by impairment of ER functioning just as it is by glutamate receptor activation.
Paschen
Wulf
W
Department of Experimental Neurology, Max-Planck-Institute for Neurological Research, Gleuelerstrasse 50, 50931 Köln, Germany. paschen@mpin-koeln.mpg.de
Mengesdorf
Thorsten
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003546:Cysteine Endopeptidases; D004533:Egtazic Acid / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D000072233:Homer Scaffolding Proteins; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology
D002352:Carrier Proteins; D002614:Chelating Agents; D004791:Enzyme Inhibitors; D000072233:Homer Scaffolding Proteins; D007976:Leupeptins; D009097:Multienzyme Complexes; D009479:Neuropeptides; D020033:Protein Isoforms; D012333:RNA, Messenger; D004533:Egtazic Acid; D019284:Thapsigargin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde; D002118:Calcium