| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2015: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2014: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Outline of Annual Research Achievements |
The kinesin superfamily proteins (KIFs) have been shown to transport various membranous organelles and protein complexes in a microtubule- and ATP-dependent manner (Hirokawa and Noda, 2008; Schliwa, 2002). In the previous research, we identified Kinesin superfamily protein 26A (KIF26A), KIF26A is a rather atypical member as it lacks ATPase activity. We found that KIF26A suppressed GDNF-Ret signaling by direct binding and inhibition of Grb2, an essential component of GDNF/Akt/ERK signaling (Zhou et al., Cell 139, 802-813, 2009).
In this study, we have occasionally noticed the hypersensitive and prolonged pain response of Kif26a-/- mouse pups during handling, and deeply investigated its cellular and molecular mechanisms.
In order to understand the molecular basis of this impairment in Ca clearance, we assessed the level of the inhibitory tyrosine phosphorylation level of PMCA by using a KIF26A knockdown system in F11 cells. As a result, the tyrosine phosphorylation level of PMCA in KD cells was significantly higher than that in control cells, which could partly explain the impairment in Ca clearance in Kif26a-/- neurons via PMCA inactivation. We investigated the levels of SFK/FAK activation. Immunocytochemistry against pFAK in Kif26a-/- neurons revealed a significantly stronger signal than that in Kif26a+/+ neurons. In other hand, immunocytochemistry against pSFK, which is a kinase further upstream to FAK, was largely unaltered. These data suggested the possibility that the SFK-to-FAK signal transduction is abnormally enhanced by KIF26A deficiency.
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