TY - JOUR
T1 - A role for ZnT-1 in regulating cellular cation influx
AU - Segal, Dror
AU - Ohana, Ehud
AU - Besser, Limor
AU - Hershfinkel, Michal
AU - Moran, Arie
AU - Sekler, Israel
N1 - Funding Information:
We thank Dr. W.F. Silverman for fruitful discussions and critical reading of the manuscript, and Ms. H. Tamir-Azriel and I. Cohen for technical help with the immunoblots. This work was partially supported by the GIF Grant 10588099.01/98 (I.S. and A.M.), ISF Grant 456/02.1 (I.S. and A.M.), ISF equipment Grant 456/02.2 (I.S.), and BSF Grant 2001101 (M.H.).
PY - 2004/10/29
Y1 - 2004/10/29
N2 - The ZnTs are a growing family of proteins involved in lowering or sequestration of cellular zinc. Using fluorescent measurements of zinc transport we have addressed the mechanism of action of the most ubiquitously expressed member of this family, ZnT-1. This protein has been shown to lower levels of intracellular zinc though the mechanism has remained elusive. The rate of zinc efflux in HEK293 cells expressing ZnT-1 was not accelerated in comparison to control cells, suggesting that ZnT-1 may be involved in regulating influx rather than efflux of zinc. Co-expression of the L-type calcium channel, a major route for zinc influx, and ZnT-1 resulted in a 3-fold reduction in the rate of zinc influx in HEK293 and PC-12 cells, indicating that ZnT-1 modulates zinc permeation through this channel. Immunoblot analysis indicates that ZnT-1 expression does not modulate LTCC expression. Our findings therefore indicate that ZnT-1 modulates the permeation of cations through LTCC, thereby, regulating cation homeostasis through this pathway. Furthermore, ZnT-1 may play a role in cellular ion homeostasis and thereby confer protection against pathophysiological events linked to cellular Ca 2+ or Zn 2+ permeation and cell death.
AB - The ZnTs are a growing family of proteins involved in lowering or sequestration of cellular zinc. Using fluorescent measurements of zinc transport we have addressed the mechanism of action of the most ubiquitously expressed member of this family, ZnT-1. This protein has been shown to lower levels of intracellular zinc though the mechanism has remained elusive. The rate of zinc efflux in HEK293 cells expressing ZnT-1 was not accelerated in comparison to control cells, suggesting that ZnT-1 may be involved in regulating influx rather than efflux of zinc. Co-expression of the L-type calcium channel, a major route for zinc influx, and ZnT-1 resulted in a 3-fold reduction in the rate of zinc influx in HEK293 and PC-12 cells, indicating that ZnT-1 modulates zinc permeation through this channel. Immunoblot analysis indicates that ZnT-1 expression does not modulate LTCC expression. Our findings therefore indicate that ZnT-1 modulates the permeation of cations through LTCC, thereby, regulating cation homeostasis through this pathway. Furthermore, ZnT-1 may play a role in cellular ion homeostasis and thereby confer protection against pathophysiological events linked to cellular Ca 2+ or Zn 2+ permeation and cell death.
KW - Ion homeostasis
KW - L-type calcium channel
KW - Neuronal zinc toxicity
KW - Zinc efflux
KW - Zinc transporter
KW - Znt-1
UR - http://www.scopus.com/inward/record.url?scp=4644223422&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2004.08.211
DO - 10.1016/j.bbrc.2004.08.211
M3 - Article
AN - SCOPUS:4644223422
SN - 0006-291X
VL - 323
SP - 1145
EP - 1150
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -