Expression and regulated nuclear transport of transducers of regulated CREB 1 in retinal ganglion cells.
Calcium- and cAMP-dependent activation of CREB and transcription of cAMP-responsive element (CRE)-target genes play critical roles in various physiological and pathological conditions. TORCs (transducers of regulated CREB) represent a new family of conserved CREB coactivators that function as intracellular calcium- and cAMP-sensitive coincidence detectors, controlling the kinetics of CRE-mediated responses and long-term potentiation of synaptic transmission. Here we examined the expression and activity-dependent translocation of TORCs in adult retinal ganglion cells (RGCs), the primary target of acute retinal ischemic injury as well as chronic retinal degenerative diseases. We found that both mRNAs of TORC1 and TORC2, but not TORC3, were enriched in adult rat retina. Comparing with TORC2, TORC1 protein was highly and selectively expressed in RGCs. At resting condition, TORC1 protein was localized in the cytoplasm but not nucleus of RGCs. Activation of N-methyl-D-aspartate (NMDA) receptors by intravitreous injection of NMDA or increase of cAMP signaling by administration of forskolin triggered nuclear accumulation of TORC1. Furthermore, transient retinal ischemic injury resulted in peri-nuclear and nuclear accumulation of TORC1 as well as transcription of BDNF in RGCs. Our results demonstrate that TORC1 is enriched in RGCs and its subcellular location could be regulated by Ca(2+) and cAMP, suggesting that manipulation of TORC1 activity may promote survival of RGCs in some optic disease conditions.
Department of Ophthalmology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, China.
J
J
Deng
X-L
XL
Zhang
J-W
JW
Wang
L-L
LL
Teng
J
J
Ge
H
H
Takemori
Z-Q
ZQ
Xiong
Y
Y
Zhou
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D015427:Reperfusion Injury / Q000503:physiopathology; D012160:Retina / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D015534:Trans-Activators; D014157:Transcription Factors / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; C545700:CRTC2 protein, rat; C519510:Crtc1 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D015534:Trans-Activators; D014157:Transcription Factors; D016202:N-Methylaspartate; D000242:Cyclic AMP