TY - JOUR
T1 - Ca2+ influx through P2X receptors induces actin cytoskeleton reorganization by the formation of cofilin rods in neurites
AU - Homma, Kohei
AU - Niino, Yusuke
AU - Hotta, Kohji
AU - Oka, Kotaro
PY - 2008/2/1
Y1 - 2008/2/1
N2 - In physiological and pathological events, extracellular ATP plays an important role by controlling several types of purinergic receptors and changing cytoskeleton dynamics. To know the process of ATP-dependent cytoskeleton remodeling, we focused on cofilin, a key regulator of actin cytoskeleton, and investigated the dynamics of cofilin in PC12 cells through fluorescent protein-labeled cofilin and actin, Ca2+ imaging, and fluorescence resonance energy transfer (FRET) techniques. As a result, ATP induced intracellular Ca2+ increase, following cofilin rods' formation. ATP-induced cofilin rods' formation was not observed in cells expressing unphosphorylatable variant of cofilin. A P2X receptor agonist, but not P2Y, induced the formation of cofilin rods, whereas calmodulin and calcineurin inhibitors suppressed it. These results indicate that Ca2+ influx through P2X receptors induces the formation of cofilin rods via calcineurin-dependent dephosphorylation of cofilin. This pathway might be one candidate to explain the effects of ATP on neuronal development and injury.
AB - In physiological and pathological events, extracellular ATP plays an important role by controlling several types of purinergic receptors and changing cytoskeleton dynamics. To know the process of ATP-dependent cytoskeleton remodeling, we focused on cofilin, a key regulator of actin cytoskeleton, and investigated the dynamics of cofilin in PC12 cells through fluorescent protein-labeled cofilin and actin, Ca2+ imaging, and fluorescence resonance energy transfer (FRET) techniques. As a result, ATP induced intracellular Ca2+ increase, following cofilin rods' formation. ATP-induced cofilin rods' formation was not observed in cells expressing unphosphorylatable variant of cofilin. A P2X receptor agonist, but not P2Y, induced the formation of cofilin rods, whereas calmodulin and calcineurin inhibitors suppressed it. These results indicate that Ca2+ influx through P2X receptors induces the formation of cofilin rods via calcineurin-dependent dephosphorylation of cofilin. This pathway might be one candidate to explain the effects of ATP on neuronal development and injury.
KW - Actin
KW - Calcium
KW - Cofilin
KW - FRET
KW - PC12
KW - Purinergic receptor
UR - http://www.scopus.com/inward/record.url?scp=38649140136&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=38649140136&partnerID=8YFLogxK
U2 - 10.1016/j.mcn.2007.10.001
DO - 10.1016/j.mcn.2007.10.001
M3 - Article
C2 - 17993279
AN - SCOPUS:38649140136
VL - 37
SP - 261
EP - 270
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
SN - 1044-7431
IS - 2
ER -