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東京大学グローバルCOE 特別セミナー開催のお知らせです。
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日時 : 平成20年6月4日(水)  13:30~14:30
場所 : 東京大学医学部教育研究棟13階第6セミナー室
講師 : Thomas LAUNEY&s_comma; PhD
所属 : 理化学研究所 脳科学総合研究センター
演題 : Shape matters: Ultrastructural analysis of Purkinje cell spines
reveals a specific and highly asymmetrical organization&s_comma; with significant
influence on molecular signal integration.
概要 : As the molecular mechanisms of synaptic plasticity are slowly
revealed&s_comma; it becomes increasingly obvious that what happens and where
it happens cannot be dissociated. In this respect&s_comma; the synaptic spine
represents a highly adapted structure for cellular signaling because
its constricted neck acts as a barrier to diffusion of cytoplasmic
proteins and second messengers. In addition&s_comma; the convoluted space
inside the spine may create micro-domains with high density of
reacting molecules&s_comma; potentially influencing the speed of intermolecular
reactions. We used three-dimensional reconstruction of electron
micrograph from serially sectioned Purkinje cell dendrites and electron
tomography to analyze the subcellular morphological features of the
spine&s_comma; at synapse between PC and parallel fibers. Specifically&s_comma; we
measured the shape and relative position in the spine of the post-synaptic
density&s_comma; the spine apparatus (smooth ER protruding into the spine) and
the organelles that may impede molecular diffusion in the spine and
dendritic shaft. This analysis showed that the PSD is systematically
located on the side of the spine head rather than at the apex&s_comma; irrespective
of the spine shape and incidence angle of the parallel fiber. The
morphology of the spine apparatus appeared to be optimized to
maximize its surface facing the PSD and facilitate signal transduction.
Similar evaluation in rat mutant devoid of spine apparatus
demonstrated that this structure plays a central role as organizer of
spine morphology. The functional consequence of this specific
cytoarchitecture on molecular signaling was evaluated using realistic
reaction-diffusion models of Inositol-3-Phosphate signaling in
reconstructed and synthetic spine morphologies. Our results suggest
that in addition to receptor/enzyme distribution and kinetic&s_comma;
the relative position of spine apparatus and PSD has drastic
consequences on the efficacy of molecular signal transmission within
the spine and may thus directly affect induction of synaptic
plasticity. This study suggests that the morphological organization
of the PC-PF synapse has a profound influence on signaling and also
provide a precise description of the various substructures for use in
molecular-level simulation.

主催:東京大学大学院医学系研究科 疾患生命工学センター
構造生理学  河西研究室



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