Skip Ribbon Commands
Skip to main content

Yasunori Saheki


 
Nanyang ​Assistant Professor Yasunori Saheki
MD, PhD
Principal Investigator, Cell Biology ​and Molecular Neuroscience Laboratory

 
 
 
 
Team

  • Dr Bilge Ercan, PhD, Research Fellow 
  • Dr Tomoki Naito, PhD, Research Fellow 
  • Dr Jingbo Sun, PhD, Research Fellow​
  • Dennis Dharmawan, Research Assistant
  • Darshini Jeyasimman, PhD Student
  • Nur Raihanah Binte Mohd Harion, PhD Student 
  • Hong Zheng (Dylan) Koh, PhD Student

Introduction


Assistant Professor Yasunori Saheki is a Nanyang Assistant Professor at Lee Kong Chian School of Medicine, Nanyang Technological University. He attended Okayama University Medical School in Okayama, Japan, obtaining his MD in 2005. He then enrolled in the David Rockefeller Graduate Program at the Rockefeller University in New York, USA. Working in the laboratory of Dr. Cori Bargmann, he investigated the mechanisms of ion channel localisation at the nerve terminals using C. elegans. After receiving his PhD in Neurobiology in 2010, Asst Prof Saheki moved to the Department of Cell Biology at the Yale University School of Medicine in New Haven, where he worked as a postdoctoral fellow in the laboratory of Dr. Pietro De Camilli, supported by fellowships from the Uehara memorial foundation and the Japan Society for the Promotion of Science. Using a combination of genome editing, biochemistry, quantitative cellular imaging, and optogenetics, he studied the regulatory mechanisms that govern cellular lipid homeostasis. He joined the faculty at LKCMedicine as a Nanyang Assistant Professor in March, 2016. He is also a Visiting Associate Professor at the Institute of Resource Development and Analysis, Kumamoto University, Japan. His laboratory employs the combination of C. elegans genetics and mammalian cell biology to tackle fundamental questions in cellular lipid regulation as well as the mechanisms that underlie neurological disorders.

 
Research Focus
  
​​​

Lipid homeostasis plays a central role in membrane integrity, signalling and cell viability in all eukaryotic cells. Dynamic transfer of lipids from one cellular compartment to another functions in this process; however, our knowledge regarding the mechanisms that control lipid delivery remains limited. The long-term goal of our laboratory is to gain mechanistic insights into how cellular lipid compartmentalisation is maintained and understand its role in specializsed cells, particularly neuronal cells. 

Lipid regulation at membrane contact sites

In eukaryote, most membrane lipids are synthesised in the endoplasmic reticulum (ER). Vesicular transport, which employs membrane budding and fusion reactions, plays an important role in delivery of newly synthesiszed lipids to other membranes. However, growing evidence suggests a critical role of non-vesicular transport in lipid exchange at membrane contact sites between the ER and other membranous organelles as well as the plasma membrane (PM). Asst Prof Saheki’s lab aim to uncover the function of membrane contact sites, with particular focus on ER-PM contacts, in order to advance our knowledge in lipid homeostasis.

Lipid homeostasis in neuronal cells
Neuronal cells extend multiple processes for efficient neurotransmission; synaptic membranes are highly dynamic and can be separated from the cell body by a significant distance. At distant nerve terminals, vesicular transport is not sufficiently rapid to replenish the loss of PM lipids. Neuronal processes, including axons and dendrites, are highly decorated with a continuous network of the ER (Figure1). Therefore, non-vesicular lipid transport via ER-PM contacts is likely to have significant roles in maintenance of the neuronal PM. Significantly, mutations in ER morphogenetic proteins have been identified in neurodegenerative disorders including motor neuron diseases. Asst Prof Saheki’s working hypothesis is that lipid regulation at ER-PM contacts is critical for the viability of neurons with particularly long axons, including motor neurons. His lab aims to elucidate the basic principle of lipid homeostasis in neuronal cells and uncover the mechanisms of the progression of neurodegeneration.

Lin​ks to neurodegeneration
The potential role of membrane contact sites in lipid exchange is fundamental for our understanding of lipid homeostasis, and these results have broad implications. Moreover, recent human genetic studies revealed the strong link between motor neuron diseases with more common neurodegenerative disorders including Parkinson’s disease, and Alzheimer’s disease. Therefore, the study of motor neuron diseases, and more generally the mechanisms of lipid regulation, may advance our understanding of other neurodegenerative disorders.

Yasunori Saheki 1-02 (Custom).jpg 

Selected Publications
 
Naito T, Ercan B, Krshnan L, Triebl A, Koh DHZ, …, Saheki Y. (2019). Movement of accessible plasma membrane cholesterol by GRAMD1 lipid transfer protein complex. eLife, pii: e51401

Bian X, Saheki Y, & De Cemilli P. (2018). Ca2+ releases E-Syt1 autoinhibition to couple ER-plasma membrane tethering with lipid transport.​ The EMBO Journal, 37:219-234.
 
Saheki Y, & De Camilli P. (2017). Endoplasmic reticulum-plasma membrane contact sites. Annual Review of Biochemistry, 86:659-84.

Saheki Y,
Bian X, Schauder CM, et al. (2016). Control of ​plasma membrane lipid homeostasis by the extended synaptotagmins. Nature Cell Biology, 5:461-3.
 
Fernández-Busnadiego R, Saheki Y, & De Camilli. P (2015). Three dimensional architecture of extended synaptotagmin-mediated ER-plasma membrane contact sites. Proceedings of the National Academy of Sciences of the United States of America, 112:4837-8.

Schauder CM, Wu X, Saheki Y, et al. (2014). Structure of a lipid-bound extended-synaptotagmin indicates a role in lipid transfer. Nature, 510:552-5.


Saheki Y, & De Camilli P. (2012). Synaptic vesicle en​docytosis. The Synapse, Chapter 5 (79-108). Cold Spring Harbor Lab Press.

Saheki Y, & Bargmann CI (2009). Presynaptic CaV2 calcium channel traffic requires CALF-1and the alpha (2) delta subunit UNC-36.​ Nature Neuroscience. 10, 1257-65. News and Views in Nat Neurosci. 10, 1213-4 (2009).
 

* Complete list of publications: Google Scholar​
​​​​
Not sure which programme to go for? Use our programme finder
Loading header/footer ...