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One path to understanding energy transduction in biological systems

Nature Medicine volume 18, pages 1478–1482 (2012)Cite this article

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Who is not fascinated by the myriad biological movements that define life? From cell migration, cell division and a network of translocation activities within cells to highly specialized muscle contraction, molecular motors operate by burning ATP as fuel. Three types of molecular motors—myosin, kinesin and dynein—and nearly 100 different subtypes transduce that chemical energy into mechanical movements to carry out a wide variety of cellular tasks. Understanding the molecular basis of energy transduction by these motors has taken decades.

Our understanding of molecular motors could be viewed as beginning with the two 1954 papers in Nature by Hugh Huxley and Jean Hanson and Andrew Huxley and Rolf Niedergerke, respectively, where the authors proposed the sliding-filament theory of muscle contraction. But a good place to start my story is 1969, when Hugh Huxley, on the basis of his remarkable X-ray diffraction experiments on live muscle coupled with electron microscopy, postulated the swinging cross-bridge hypothesis of muscle contraction1. Thus, more than 40 years ago, he proposed the basic concepts of how the myosin molecule produces the sliding of actin filaments to produce contraction. Hugh Huxley laid the foundation for the molecular motor field, and we are all indebted to him.

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Figure 1: Woods Hole Physiology Course, 1963.
Figure 2: Many of the contributors to the discoveries regarding energy transduction by myosins and the roles of myosins in nonmuscle cells.
Figure 3: Dictyostelium has a muscle-like myosin and membrane-associated actin.
Figure 4: One approach to an in vitro motility assay from a totally defined system.
Figure 5: The actin-activated myosin chemomechanical cycle.
Figure 6: In vitro motility taken to the single-molecule level using the physics of laser trapping.

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Acknowledgements

Discoveries in science are a community enterprise involving scores of investigators making pivotal contributions along the way. In this short essay, I have necessarily left out the names of many people who contributed to the breakthroughs we made on the workings of cellular motors. I thank all the members of my laboratory over these many years, with whom I have shared the joys of discovery. My mentors have my gratitude for their support and encouragement and for sharing with me their own ways of creative research. It has also been my privilege to share the excitement of discoveries with my fellow faculty colleagues first at the University of California–San Francisco and for the last 35 years at Stanford University. I also thank K. VijayRaghavan, S. Mayor and my colleagues at the National Center for Biological Sciences, Bangalore for incorporating me into their inspiring and innovative scientific activities for the last ten years. And my immense gratitude goes to my family, first and foremost to my wife Anna for bringing her energy, keen intellect and unwavering support into my life. My daughters Rani and Serena carry on the values my parents imparted to me, and they, together with my erudite sons-in-law Dan and Dave and my 'cool' grandchildren Indira, Hana, Anjali, Alexander and Nathaniel, are the joys of my life. Our work would not have been possible without the generous financial support from the US National Institutes of Health and grants from the Human Frontiers Science Program.

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  1. Department of Biochemistry, Stanford University School of Medicine, Stanford, California, USA

    James A Spudich

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Correspondence to James A Spudich.

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Spudich, J. One path to understanding energy transduction in biological systems. Nat Med 18, 1478–1482 (2012). https://doi.org/10.1038/nm.2924

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