Regulated expression of the Ras effector Rin1 in forebrain neurons.
The Ras effector Rin1 is induced concomitant with synaptogenesis in forebrain neurons, where it inhibits fear conditioning and amygdala LTP. In epithelial cells, lower levels of Rin1 orchestrate receptor endocytosis. A 945 bp Rin1 promoter fragment was active in hippocampal neurons and directed accurate tissue-specific and temporal expression in transgenic mice. Regulated expression in neurons and epithelial cells was mediated in part by Snail transcriptional repressors: mutation of a conserved Snail site increased expression and endogenous Snai1 was detected at the Rin1 promoter. We also describe an element closely related to, but distinct from, the consensus site for REST, a master repressor of neuronal genes. Conversion to a consensus REST sequence reduced expression in both cell types. These results provide insight into regulated expression of a neuronal Ras effector, define a promoter useful in telencephalic neuron studies, and describe a novel REST site variant directing expression to mature neurons.
Dzudzor
Bartholomew
B
Department of Biological Chemistry, Molecular Biology Institute and Jonsson Cancer Center, David Geffen School of Medicine at UCLA, 615 Charles E. Young Drive, 34609 BSRB, Los Angeles, CA 90095-1737, USA.
Huynh
Lucia
L
Thai
Minh
M
Bliss
Joanne M
JM
Nagaoka
Yoshiko
Y
Wang
Ying
Y
Ch'ng
Toh Hean
TH
Jiang
Meisheng
M
Martin
Kelsey C
KC
Colicelli
John
J
D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011401:Promoter Regions, Genetic; D016548:Prosencephalon / Q000166:cytology* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; C490451:Rin1 protein, mouse; C000604407:SNAI1 protein, human; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D020691:rab GTP-Binding Proteins