Zinc homeostatic proteins in the CNS are regulated by crosstalk between extracellular and intracellular zinc.
Release of Zn(2+) from presynaptic glutamatergic terminals has long been considered the principle challenge necessitating the existence of zinc homeostatic proteins (ZHP) in the mammalian nervous system. It is now known that neural cells also possess an intracellular zinc pool, termed here [Zn(2+)](i), which functions in a cell signaling context. A major challenge is characterizing the interaction of these two populations of zinc ions. To assess the relationship of this Zn(2+) pool to cellular ZHP production, we employed immunofluorescence and immunoblot analysis to compare the expression of ZHP's ZnT-1 and MT-I/II in olfactory bulb and hippocampus of wild-type and ZnT-3 KO mice, which lack synaptic Zn(2+). In both areas, the respective distribution and concentration of ZnT-1 and MT-I/II were identical in ZnT-3 KO and control animals. We subsequently examined ZHP content in ZnT-3 KO and WT mice treated with a membrane-permeable Zn(2+) chelator. In both olfactory bulb and hippocampus of the KO mice, the ZHP content was significantly reduced 15 h after chelation of [Zn(2+)](i) compared to WT controls. Our findings support the conclusion that ZHP expression is regulated by crosstalk between synaptic and intracellular pools of Zn(2+).
Karol
Natalya
N
Department of Morphology, Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Brodski
Claude
C
Bibi
Yuval
Y
Kaisman
Tehila
T
Forberg
Michal
M
Hershfinkel
Michal
M
Sekler
Israel
I
Silverman
William F
WF
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002490:Central Nervous System / Q000033:anatomy & histology / Q000378:metabolism*; D002614:Chelating Agents / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006706:Homeostasis; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000502:physiology; D013569:Synapses / Q000378:metabolism; D015032:Zinc / Q000378:metabolism*
D002352:Carrier Proteins; D027682:Cation Transport Proteins; D002614:Chelating Agents; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C491054:Mt2 protein, mouse; C485803:Slc30a1 protein, mouse; C491177:Slc30a3 protein, mouse; C525355:metallothionein-1, mouse; D008668:Metallothionein; D015032:Zinc