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van Tolの研究室の周防諭博士にセミナーをお願いしました。モノアミン神経伝達物質


日時:平成18年11月28日(火) 15:00-16:00
演者:Dr. Satoshi Suo(周防 諭)
(Hubert H.M. Van Tol Lab&s_comma; Centre for Addiction & Mental Health&s_comma; University
of Toronto&s_comma; 250 College Street&s_comma; Toronto&s_comma; Ontario&s_comma; M5T 1R8&s_comma; Canada)
講演タイトル:"Amine neurotransmitter signaling in C. elegans"
cAMP response element binding protein (CREB) is a signal-activated
transcription factor&s_comma; which induces gene expression downstream of CRE upon
its activation to control a broad range of biological processes. In C.
elegans&s_comma; the CREB activation can be visualized using a transgenic strain
carrying a transcriptional reporter in which CRE is fused to a GFP reporter
(cre::gfp). Using the cre::gfp reporter strain&s_comma; we found that starvation
induces CREB activation in the SIA neurons. The octopamine-deficient mutant
tbh-1 did not show CREB activation upon starvation and the exogenous
application of octopamine resulted in CREB activation in well-fed animals&s_comma;
indicating that octopamine is responsible for the starvation-mediated CREB
activation. We also found that the octopamine receptor&s_comma; Gq&s_comma; and CREB work
in the SIA neurons to activate the CRE-mediated gene expression while Go
and CaMKII suppress it.
Dopamine in C. elegans is shown to be involved in food (bacteria) sensing.
Mechanosensory dopaminergic neurons sense bacteria and activate dopamine
signaling in the presence of food. We tested whether dopamine signaling
interacts with the octopamine signaling. Exogenous application of dopamine
suppressed the exogenous octopamine-mediated CREB activation. Moreover&s_comma;
dopamine-deficient mutant cat-2 showed spontaneous CREB activation in SIA
neurons in the presence of food while cat-2;tbh-1 double mutants did not.
We also found that Gi/o-coupled dopamine receptors were involved in the
dopamine signaling. The results suggest that the dopamine signal is
suppressing the octopamine signal in the presence of food and the
octopamine signal is activated when the dopamine signal ceases in the
absence of food. We also demonstrate that the dopamine-octopamine signaling
regulates the acetylcholine release likely through the regulation of CREB
in the SIA neurons.
This study provides new insight in the in vivo molecular mechanisms of the
amine neurotransmitter-mediated signaling and describes the interaction
between the neurotransmitter signalings that allows animals to respond to
environmental stimuli.