Prof. Sumio Terada
ISP2012 Lecture Course Abstract:
Microscopic and spectroscopic dissections of cytosolic and cytoskeletal protein dynamics in neurons
Neuronal cells such as neurons and glial cells are atypical and asymmetric in their morphology; both of them having long processes. They have to endure the burden of energy-consuming long-distance intracellular transport, and develop specialized cytoskeletal structures. Both intracellular transport and cytoskeletal dynamics are inseparably interrelated, and essential for cellular homeostasis and function. In neurons, these cytoskeletal protein transport and dynamics have been investigated as a slow axonal transport study. This lecture will explain its brief history with special reference to microscopic and spectroscopic techniques that we have experienced.
Based on the classic pulse labeling studies, especially regarding cytoskeletal proteins on slow axonal transport, Lasek’s group proposed the cytoskeletal polymer sliding theory as a possible slow axonal transport mechanisim. They considered the polymer sliding as a prerequisite for slow axonal transport of other general cytosolic proteins, and further claimed “structural hypothesis” that defines the polymer sliding for other cytosolic proteins to ride piggy-back. On the other hand, Ochs’s group insisted “unitay hypothesis” that can explain various slow axonal transport rates with a single putative motor origin. They speculated that the variation of the transport rates might reflect (1) the different affinity between cytosolic-protein cargoes and a putative motor molecule and/or (2) the changing interaction beween transporting complex and intraaxonal environments. “Unitary hypothesis” is based on the cytoskeletal subunit transport theory, because the moving cytoskeletal proteins pulse-labeled were contained mainly in the biochemcally soluble fractions. Following studies implicated that the motor molecule for slow transport is Kinesin-1, the same motor for fast axonal tranport of membranous organelles. These lines of evidence justified the “unitary hypothesis” over the “structural hyphthesis” but the dispute between polymer sliding and subunit transport theories has not fully been resolved yet.
In this lecture, I will address the controversies and their possible solutions, mainly based on our experimental evidences.
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- Ochs S: J Physiol 253, 459-475, 1975.
- Okabe S et al.: J Cell Biol 121, 375-386, 1993.
- Takeda S et al.: J Cell Biol 127, 173-185, 1994.
- Terada S et al.: Science 273, 784-788, 1996.
- Terada S et al.: Cell 103, 141-155, 2000.
- Yabe JT et al.: J Cell Sci 112, 3799-3814, 1999.
- Xia CH et al.: J Cell Biol 161, 55-66, 2003.
- Wang L et al.: Nat Cell Biol 2, 137-141, 2000.
- Wang L, Brown A: Mol Biol Cell 12, 3257-3267, 2001.
- Yan Y, Brown A: J Neurosci 25, 7014-7021, 2005.
- Yuan A et al.: J Neurosci 29, 11316-11329, 2009.
- Terada S et al.: EMBO J 29, 843-854, 2010
- Prof. Terada's ISP2012 Profile
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