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Axonal/Dendritic Growth and Circuit Formation

開催日 2014/9/13
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Importance of the inositol 1,4,5-trisphosphate receptor type 3 (IP3R3) in growth cone navigation

  • P3-073
  • Carmen Chan:1 Hiroki Akiyama:1 Toru Matsu-ura:2 Katsuhiko Mikoshiba:2 Hiroyuki Kamiguchi:1 
  • 1:RIKEN Brain Science Institute, Lab. for Neuronal Growth Mechanisms 2:RIKEN Brain Science Institute, Developmental Neurobiology 

The growth cone can be thought of as the 'hand and eye' of a developing axon - one that possesses both sensory and motor functions. As a bridge between these two, the second messenger, calcium ion (Ca2+), is released upon guidance cue-receptor engagement, and instructs the growth cone turning machinery on the direction of turning.

The inositol 1,4,5-trisphosphate (IP3) receptor (IP3R) is one of the two major classes of Ca2+ channels that release Ca2+ from internal storage. Our lab has previously shown that after nerve growth factor (NGF) bound to and activated cell surface receptors, the resultant generation of IP3 formed a gradient across the growth cone (high on the side facing the NGF source, i.e. the 'near side'). IP3 activated IP3R, and in turn created a gradient of Ca2+ elevation inside the growth cone. Such asymmetric Ca2+ signal enabled attractive growth cone turning.

In vertebrates, there are three separate genes coding for three IP3R subtypes. My data show that IP3R type 3 (IP3R3) is necessary for the NGF turning response. In vitro , growth cones from IP3R3 knockout mice migrate straight forwards rather than turning towards the source of NGF, as in wildtype growth cones. Surprisingly, these IP3R3 knockout growth cones are still able to generate Ca2+ elevations in response to NGF. However, the Ca2+ signal spreads to the far side, in contrast to the wildtype counterpart in which Ca2+ elevation is localized to the near side only. These data indicate that IP3R3 is needed for the asymmetry in the Ca2+ response, and thus for growth cone turning.

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