Guy M Benian, MD
Muscle Cell Biology
Pathology & Laboratory Medicine
Professor, Department of Cell Biology, Emory University
Email Address: email@example.com
B.S. University of Michigan, Ann Arbor, MI, high honors & high distinction, - 1976
M.D. Wayne State University School of Medicine, Detroit, MI, - 1980
Resident Laboratory Medicine, Barnes Hospital and Washington University, St. Louis, MO, 1980 - 1985
Postdoc Fellow Department of Genetics, Washington University, St. Louis, MO, supervisor R.H Waterston, 1981 - 1986
- Using C. elegans to study the assembly and maintenance of the sarcomere The sarcomere performs the work of muscle contraction and is a "nano"-machine consisting of a highly ordered assemblage of at least several hundred proteins. Despite ever increasing knowledge of the components and functions of sarcomeric proteins (indeed new ones are discovered each year!), we still don't understand how sarcomeres are assembled, and maintained in the face of muscle contraction. Our lab is studying these questions in the model genetic organism, C. elegans. C. elegans is a superb platform for discovery of new and conserved sarcomeric components, and for learning new information about already known components. We are focused on two questions: (1) What are the structures and functions of the giant muscle proteins (>700,000 Da)? (2) What are the molecular mechanisms by which sarcomeres are attached to the muscle cell membrane and transmit force? Our approaches involve genetics, cell biology and biochemistry. Our studies benefit from collaborations with structural biologists, biophysicists and biomedical engineers. Our studies have relevance for understanding the molecular mechanisms of human inherited diseases of skeletal and heart muscle, including muscular dystrophies, myopathies and cardiomyopathies. The giant muscle proteins consist primarily of multiple copies of immunoglobulin (Ig) and fibronectin type 3 (Fn3) domains, and one or even two protein kinase domains. In C. elegans, there are 3 such proteins, twitchin (754,000 Da, located in the sarcomeric A-band, and one function likely to be regulation of muscle relaxation), TTN-1 (2.2 MDa, located in the I-band and perhaps acting as a molecular spring), and UNC-89 (up to 900,000 Da, a homolog of the human protein obscurin, and having a role in the assembly/maintenance of the M-line). One aim is determining the identity of proteins that interact with these giants that explains their localization and their functions. Other goals including learning the substrates of the protein kinase domains, and to understand how the normally"autoinhibited" kinase domains become activated (in collaboration with Dr. Olga Mayans, University of Konstanz, Germany and Dr. Hang Lu, Georgia Tech.). By cloning mutationally-defined genes, conducting 2-hybrid screens, and localizing proteins with antibodies and GFP fusions, we are defining complex protein interaction networks at muscle attachment sites. We are testing the hypothesis that proteins at the attachment sites are involved in transmitting the force of muscle contraction to the outside of the cell. One project is to understand the molecular mechanism by which one of these proteins, UNC-112 (kindlin in humans), becomes localized to muscle attachment sites. Finally, in collaboration with Dr. Andres Oberhauser (UTMB), we are beginning to study the mechanism by which the conserved protein UNC-45 acts as a chaperone for the folding of the myosin head domain, and how UNC-45 may also repair damaged myosin heads in already established sarcomeres. We are very grateful for grant support from the Human Frontier Science Program and the NIH.
Honors / Awards:
- The Shur Award for Outstanding Teaching, Department of Cell Biology, 2018
- Outstanding Service Award, Emorys Graduate Program in Genetics and Molecular Biology, 2005-2006
- Established Investigator Award, American Heart Association, 1991-1996
- Muscular Dystrophy Association Postdoctoral Fellow, 1982 & 1983
- B.S. w/ high honors, University of Michigan, 1976
Selected/Most Recent Publications:
Published and Accepted Research Articles -
- Williams RM, Franke B, Wilkinson M, Fleming JR, Rigden DJ, Benian GM, Eyers PA, Mayans O. Autophosphorylation is a mechanism of inhibition in twitchin kinase. J. Mol. Biol. 430, 793-805, 2018.
- Qadota H, Matsunaga Y, Bagchi P, Lange KI, Carrier KJ, Vander Pols W, Swartzbaugh E, Wilson KJ, Srayko M, Pallas DC, Benian GM. Protein phosphatase 2A is crucial for sarcomere organization in C. elegans striated muscle. Mol Biol Cell, 29: 2084-2097, 2018.
- Loveless T, Qadota H, Benian GM, Hardin J. C. elegans SORB-1 localizes to integrin adhesion sites and is required for organization of sarcomeres and mitochondria in myocytes. Mol. Biol. Cell, 28, 3621-3633, 2017 (chosen by editors for cover art)
- Qadota H, Matsunaga Y, Nguyen K, Mattheyses A, Hall DH, Benian GM. High resolution imaging of muscle attachment structures in C. elegans, Cytoskeleton 74: 426-442, 2017 (chosen by editors for cover art)
- Sonowal R, Swimm A, Sahoo A, Luo L, Matsunaga Y, Wu Z, Bhingarde JA, Ejzak EA, Ranawade A, Qadota H, Powell DN, Capaldo CT, Flacker JM, Jones RM, Benian GM, Kalman D. Indoles from commensal bacteria extend healthspan. Proc Natl Acad Sci U S A. 2017 Aug 21. pii: 201706464. doi: 10.1073/pnas.1706464114. [Epub ahead of print]
- Yohei Matsunaga, Hyundoo Hwang, Barbara Franke, Rhys Williams, McKenna Penley, Hiroshi Qadota, Hong Yi, Levi T. Morran, Hang Lu, Olga Mayans, and Guy M. Benian. Twitchin kinase inhibits muscle activity. Mol. Biol. Cell 28, 1591-1600, 2017
- Matsunaga Y, Honda Y, Honda S, Iwasaki T, Qadota H, Benian GM, Kawano T. Diapause is assoicated with a change in the polarity of secretion of insulin-like peptides. Nature Comm. 7:10573 DOI: 10.1038/ncomms10573
- Gieseler K, Qadota H, Benian GM: Development, structure and maintenance of C. elegans body wall muscle (August 23, 2016), WormBook, ed. The C. elegans Research Community, WormBook, doi/10.1895/wormbook.1.81.2, http://www.wormbook.org
- Hiroshi Qadota, Olga Mayans, Yohei Matsunaga, Jonathan L. McMurry, Kristy J. Wilson, Grace E. Kwon, Rachel Stanford, Kevin Deehan, Tina L. Tinley, Verra M. Ngwa and Guy M. Benian (2016).The SH3 domain of UNC-89 (obscurin) interacts with paramyosin, a coiled-coil protein, in C. elegans muscle. Mol. Biol. Cell 27: 1606-1620.
- Hwang H, Barnes DE, Matsunaga Y, Benian GM, Ono S, and Lu H (2016). Muscle contraction phenotypic analysis enabled by optogenetics reveals functional relationships of sarcomere components in Caenorhabditis elegans. Scientific Reports, 6:19900, DOI: 10.1038/srep19900
- Matsunaga Y, Qadota H, Furukawa M, Choe H, Benian GM. Twitchin kinase interacts with MAPKAP kinase 2 in C. elegans striated muscle. Mol. Biol. Cell. 26: 2096-2111 (2015).
- Qadota H, Luo Y, Matsunaga Y, Park AS, Gernert KM, Benian GM: Suppressor mutations suggest a surface on PAT-4 (ILK) that interacts with UNC-112 (Kindlin), J. Biol. Chem. 289, 14252-14262, 2014
- Hwang H, Krajniak J, Matsunaga Y, Benian GM, Lu H. On-demand optical immobilization of Caenorhabditis elegans for high-resolution imaging and microinjection. Lab on a Chip, 2014, in press
- Qadota H, and Benian GM. An approach for exploring interaction between two proteins in vivo (a review). Frontiers in Physiol. April 2014, volume 5, article 162
- Warner A, Xiong G, Qadota H, Rogalski T, Vogl AW, Moerman DG, and Benian GM: CPNA-1, a copine domain protein, is located at integrin adhesion sites, and is required for myofilament stability in C. elegans, Mol. Biol. Cell 24: 601-616, 2013.
Other Publications -
- Benian GM and Mayans O. Commentary (invited): Titin and obscurin: giants holding hands and discovery of a new Ig domain subset. J. Mol. Biol. 427: 707-714, 2015.
- Wilson K.J., Qadota H., and Benian G.M. Immunofluorescent localization of proteins in C. elegans muscle. In: Methods in Molecular Biology vol. 798, Myogenesis: Methods and Protocols, J.X. DiMario, ed., Humana Press, 2012.
- Bernstein S.I. and Benian G.M. Guest Editor's Introduction: Introduction to methods in invertebrate muscle biology. Methods 56, 1-2, 2012.
- Qadota H, Benian GM: Molecular structure of sarcomere-to-membrane attachment at M-lines in C. elegans muscle. (Review). J. Biomed. Biotech. volume 2010, article ID 864749, doi:10.1155/2010/864749
- Ferrara TM, Flaherty DB, and Benian GM: Titin / connectin-related proteins in C. elegans: A review and new findings, J. Mus. Res. and Cell Motil. 26: 435-447, 2005.
- Chamberlain JS and Benian GM: Muscular dystrophy: The worm turns to genetic disease, Current Biology 10: R795-R797, 2000.
- Benian GM, Ayme-Southgate A, and Tinley TL: The genetics and molecular biology of titin/connectin-like proteins in invertebrates, Reviews of Physiology, Biochemistry and Pharmacology 138: 235-268, 1999.
- Benian GM, Tang X, and Tinley TL: Twitchin and related giant Ig superfamily members of C. elegans and other invertebrates (In: Muscle Elastic Proteins), Advances in Biophysics 33:183-197, 1996.