Tomoyo Hamada, Ph.D.
Postdoctoral research fellow

Education
Okayama University, Okayama, Japan, 2003

Lab
Noriaki Ikemoto

Research Interests
EC coupling – Ryanodine receptor (RyR)

The ryanodine receptor (RyR) is a large molecule (a subunit is about 560 kDa) and Ca2+ release channel as a homotetramer in sarcoplasmic membrane. In skeletal muscle, the excitation of the transverse tubular system (T-tubule) membrane is sensed by the voltage-gated Ca2+ channel (DHPR), and the signal is transmitted to the RyR, and then RyR opens leading to Ca2+ release. The RyR is also regulated by many molecules (Ca2+, Mg2+, ATP, CaM etc.) and pharmacological reagents. Therefore, there must be intricate mechanisms, which mediate the transmission of various signals received at various sites of the RyR to its channel domain. However the intra-molecular signal transduction mechanism is unknown well.

We have provided a hypothesis, “domain-domain interaction”, which N-terminal domain and central domain of the RyR are contacted in the closed-state of the channel (zipping), while the removal of this interaction (unzipping) causes the channel activation. This hypothesis is confirmed by our recent study of the domain peptide derived fluorescence probes.

Now we are trying to monitor the molecular dynamics not only by using the fluorescence probe, but also anti-domain peptide antibodies to understand the intra- or inter-molecular mechanism of the RyR.

Recent Publications:
T. Hamada, Y. Sakube, J. Ahnn, D.-H. Kim and H. Kagawa. (2002) Molecular dissection, tissue localization and Ca2+ binding of the ryanodine receptor of Caenorhabditis elegans.  J. Mol. Biol. 324, 123-135

Contact Info
email: hamada@bbri.org, tel. 617-658-7796