Lateral diffusion of inositol 1,4,5-trisphosphate receptor type 1 is regulated by actin filaments and 4.1N in neuronal dendrites

Kazumi Fukatsu, Hiroko Bannai, Songbai Zhang, Hideki Nakamura, Takafumi Inoue, Katsuhiko Mikoshiba

研究成果: Article

71 被引用数 (Scopus)

抄録

Inositol 1,4,5-trisphosphate receptor typel (IP3R1) plays an important role in neuronal functions; however, the lateral diffusion of IP 3R1 on the endoplasmic reticulum membrane and its regulation in the living neurons remain unknown. We expressed green fluorescent protein-tagged IP3R1 in cultured rat hippocampal neurons and observed the lateral diffusion by the fluorescence recovery after photobleaching technique. IP 3R1 showed lateral diffusion with an effective diffusion constant of ∼0.3 μm2/s. Depletion of actin filaments increased the diffusion constant of IP3R1, suggesting that the diffusion of IP 3R1 is regulated negatively through actin filaments. We also found that protein 4.1N, which binds to IP3R1 and contains an actin-spectrin-binding region, was responsible for this actin regulation of the IP3R1 diffusion constant. Overexpression of dominant-negative 4.1N and blockade of 4.1N binding to IP3R1 increased the IP3R1 diffusion constant. The diffusion of IP3R type 3 (IP3R3), one of the isoforms of IP3Rs lacking the binding ability to 4.1N, was not dependent on actin filaments but became dependent on actin filaments after the addition of a 4.1N-binding sequence. These data suggest that 4.1N serves as a linker protein between IP3R1 and actin filaments. This actin filament-dependent regulation of IP3R1 diffusion may be important for the spatiotemporal regulation of intracellular Ca2+ signaling.

本文言語English
ページ(範囲)48976-48982
ページ数7
ジャーナルJournal of Biological Chemistry
279
47
DOI
出版ステータスPublished - 2004 11 19
外部発表はい

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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