Aberrant trafficking of the high-affinity choline transporter in AP-3-deficient mice

Hidemi Misawa, Hirofumi Fujigaya, Takashi Nishimura, Yasuhiro Moriwaki, Takashi Okuda, Koichiro Kawashima, Kazuko Nakata, Alicia M. Ruggiero, Randy D. Blakely, Fubito Nakatsu, Hiroshi Ohno

研究成果: Article査読

9 被引用数 (Scopus)

抄録

The high-affinity choline transporter (CHT) is expressed in cholinergic neurons and efficiently transported to axon terminals where it controls the rate-limiting step in acetylcholine synthesis. Recent studies have shown that the majority of CHT is unexpectedly localized on synaptic vesicles (SV) rather than the presynaptic plasma membrane, establishing vesicular CHT trafficking as a basis for activity-dependent CHT regulation. Here, we analyse the intracellular distribution of CHT in the adaptor protein-3 (AP-3)-deficient mouse model mocha. In the mocha mouse, granular structures in cell bodies are intensely labelled with CHT antibody, indicating possible deficits in CHT trafficking from the cell body to the axon terminal. Western blot analyses reveal that CHT on SV in mocha mice is decreased by 30% compared with wild-type mice. However, no significant difference in synaptosomal choline uptake activity is detected, consistent with the existence of a large reservoir pool for CHT. To further characterize CHT trafficking, we established a PC12D-CHT cell line. In this line, CHT is found associated with a subpopulation of synaptophysin-positive synaptic-like microvesicles (SLMV). The amounts of CHT detected on SLMV are greatly reduced by treating the cell with agents that halt AP-dependent membrane trafficking. These results demonstrate that APs have important functions for CHT trafficking in neuronal cells.

本文言語English
ページ(範囲)3109-3117
ページ数9
ジャーナルEuropean Journal of Neuroscience
27
12
DOI
出版ステータスPublished - 2008 6

ASJC Scopus subject areas

  • 神経科学(全般)

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