Frontier Research Institute for Interdisciplinary Sciences
Tohoku University

We are interested in the molecular mechanism of cellular morphogenesis. Neurons are suitable for studying the cellular morphogenesis because they are highly polarized cells. Neurons receive extracellular information with dendrites and/or cilia and transmit them to other neurons with a long axon. The elaborated cellular structure of neurons are archived by the regulation of cytoskeletal networks and the intracellular transport. However, it remains unknown how these two processes are coordinated. We have found that both processes are regulated by Kinesin Superfamily molecular motors (KIFs) (ref. 1). Cytoskeletal networks are mainly composed of microtubules. We found that microtubules are regulated by microtubule depolymerizing kinesins (KIF2A and KIF19) (ref. 2 and 3) and microtubule stabilizing kinesin (KIF26A) (ref. 4). Intracellular transport is mediated by molecular motors such as KIF1A/KIF1B, KIF13A and KIF16B (ref.5, 6,7). In addition, we found disruption of these processes leads to neuronal diseases (ref. 8). Now, we are interested in (1) the relationship between the physical property of each molecular motors and their functions in neuronal morphogenesis (2) how these multiple motors are coordinated to generate a cellular structure. Moreover, based on these findings, we are developing a new method to regulate microtubule networks.

References

1. Hirokawa, Noda, Tanaka and Niwa (2009) Nat. Rev. Mol. Cell Biol.

2. Noda* and Niwa* et al. (2012) PNAS (*equal contribution)

3. Niwa et al. (2012) Dev Cell

4. Zhou* and Niwa* et al. (2009) Cell (*equal contribution)

5. Niwa et al. (2008) Nat. Cell Biol.

6. Zhou* and Niwa* et al. (2013) Cell Reports (*equal contribution)

7. Farkhondeh, Niwa et al. (2015) J. Neurosci.

8. Niwa* and Takahashi* et al. (2013) EMBO J. (*equal contribution)

Niwa S. "The nephronophthisis-related gene ift-139 is required for ciliogenesis in Caenorhabditis elegans" (2016) Scientific Reports

Niwa S., Lipton DM., Morikawa M., Zhao C., Hirokawa N., Lu H., Shen K. "Autoinhibition of a neuronal kinesin UNC-104/KIF1A regulates the size and density of synapses" (2016) Cell Reports

Tanaka Y.,* Niwa S.*, Dong M.* (equal contribution), Farkhondeh A., Wang L., Zhou R., and Hirokawa N. "The molecular motor KIF1A transports the TrkA neurotrophin receptor and is essential for sensory neuron survival and function." (2016) Neuron