Deficiency in parvalbumin, but not in calbindin D-28k upregulates mitochondrial volume and decreases smooth endoplasmic reticulum surface selectively in a peripheral, subplasmalemmal region in the soma of Purkinje cells.
The Ca(2+)-binding proteins parvalbumin (PV) and calbindin D-28k (CB) are key players in the intracellular Ca(2+)-buffering in specific cells including neurons and have profound effects on spatiotemporal aspects of Ca(2+) transients. The previously observed increase in mitochondrial volume density in fast-twitch muscle of PV-/- mice is viewed as a specific compensation mechanism to maintain Ca(2+) homeostasis. Since cerebellar Purkinje cells (PC) are characterized by high expression levels of the Ca(2+) buffers PV and CB, the question was raised, whether homeostatic mechanisms are induced in PC lacking these buffers. Mitochondrial volume density, i.e. relative mitochondrial mass was increased by 40% in the soma of PV-/- PC. Upregulation of mitochondrial volume density was not homogenous throughout the soma, but was selectively restricted to a peripheral region of 1.5 microm width underneath the plasma membrane. Accompanied was a decreased surface of subplasmalemmal smooth endoplasmic reticulum (sPL-sER) in a shell of 0.5 microm thickness underneath the plasma membrane. These alterations were specific for the absence of the "slow-onset" buffer PV, since in CB-/- mice neither changes in peripheral mitochondria nor in sPL-sER were observed. This implicates that the morphological alterations are aimed to specifically substitute the function of the slow buffer PV. We propose a novel concept that homeostatic mechanisms of components involved in Ca(2+) homeostasis do not always occur at the level of similar or closely related molecules. Rather the cell attempts to restore spatiotemporal aspects of Ca(2+) signals prevailing in the undisturbed (wildtype) situation by subtly fine tuning existing components involved in the regulation of Ca(2+) fluxes.
Chen
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G
University of Fribourg, Division of Histology, Department of Medicine, University of Fribourg, 14, chemin du Musée, CH-1705 Fribourg, Switzerland.
Racay
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P
Bichet
S
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Celio
M R
MR
Eggli
P
P
Schwaller
B
B
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D064026:Calbindins; D002118:Calcium / Q000378:metabolism; D002525:Cerebellar Cortex / Q000166:cytology; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D004721:Endoplasmic Reticulum / Q000473:pathology* / Q000648:ultrastructure*; D005455:Fluorescent Antibody Technique / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D010320:Parvalbumins / Q000172:deficiency*; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism; D011689:Purkinje Cells / Q000473:pathology / Q000648:ultrastructure*; D064030:S100 Calcium Binding Protein G / Q000235:genetics; D018709:Statistics, Nonparametric
D064026:Calbindins; D010320:Parvalbumins; D064030:S100 Calcium Binding Protein G; D053499:Plasma Membrane Calcium-Transporting ATPases; D002118:Calcium