I. Cytoskeletal Intermediate Filaments
II. Nuclear Lamins
Part I: Cytoskeletal Intermediate Filaments
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In Part 1 of his talk, Dr. Goldman introduces us to cytoskeletal intermediate filaments beginning with an overview of IF formation and properties. Goldman focuses on vimentin to demonstrate that the assembly and disassembly of IFs are critical to cell shape change, lamellipodia formation and cell motility. Further experiments show that IF assembly and disassembly are regulated by kinases and phosphatases acting in response to growth factors and other signals.
In the second part of his talk, Goldman focuses on the nuclear lamins-a family of IFs found in the nucleus. Lamins have many critical roles including being a major determinant of nuclear size and structure. They are also necessary for DNA synthesis and repair and transcription by RNA polymerase II. Mutations in the lamin A gene are responsible for an astounding number of human diseases including the devastating early aging syndrome Hutchison Gilford Progeria. Studies of the nuclei from progeria cells are leading to a better understanding of the role of lamins in this disease and hope for treatment in the future.
Bob Goldman is Professor and Chair of the Department of Cell and Molecular Biology at the Feinberg School of Medicine at Northwestern University. He also has been a summer investigator at the Marine Biological Laboratory (MBL) in Woods Hole, since 1977.
Goldman received his Ph.D. in biology from Princeton University. He was a postdoctoral fellow at Hammersmith Hospital in London and at the MRC Institute of Virology in Glasgow where he first became interested in intermediate filaments. Goldman’s lab has continued to study the structure, function and dynamics of IFs and recently made important contributions to the understanding of Hutchison-Gilford progeria and giant axonal neuropathy, devastating childhood diseases caused by defects in IF function.
Goldman is a member of numerous advisory and editorial boards. He has been closely involved in summer education at the MBL and was the first director of the MBL’s Whitman Center for Visiting Research. He is also a past president of the American Society for Cell Biology.
- Julie Theriot iBioSeminar: The Universal Cytoskeleton
- Ron Vale iBioSeminar: Introduction to Motor Proteins
- Tony Hyman iBioSeminar: Organization of the Cytoplasm
Cytoskeletal Intermediate Filaments Primary Papers
Guo, M., et al. (2013) The Role of Vimentin Intermediate Filaments in Cortical and Cytoplasmic Mechanics. Biophys. J. 105: 1563-1568.
Mahammad, S., et al. (2013) Giant Axonal Neuropathy-Associated Gigaxonin Mutations Impair Intermediate Filament Protein Degradation. J Clin Investigation. 123: 1964-1975.
Helfand, B et al (2011) Vimentin organization modulates the formation of lamellipodia. MBOC 22: 1274-1289.
Mendez, et al (2010) Vimentin induces changes in cell shape, motility, and adhesion during the epithelial to mesenchymal transition. FASEB J 24: 1838-1851.
Helfand, B et al (2002) A requirement for cytoplasmic dynein and dynactin in intermediate filament network assembly and organization. J Cell Biol. 157: 795-806.
Prahlad, V et al (1998) Rapid Movements of Vimentin on Microtubule Tracks: Kinesin-dependent Assembly of Intermediate Filament Networks J Cell Biol. 143: 159-170.
Cytoskeletal Intermediate Filaments Reviews:
Chang, L et al (2004) Intermediate Filaments Mediate Cytoskeletal Crosstalk Nature Rev Molec Cell Biol. 5: 601-613.
Godsel, L. et al (2007) Intermediate filament assembly: dynamics to disease. Trends in Cell Biol Goldman, RD, et al (2008) Intermediate filaments: versatile building blocks of cell structure Curr Op Cell Biol 20: 2028-2034
Eriksson, J. E. et al. (2009) Introducing Intermediate Filaments: from Discovery to Disease. J Clin Investigation 119: 1673-1771.
Herrmann, H. et al (2009) Intermediate filaments: primary determinants of cell architecture and plasticity. J Clin Investigation 119: 1772-1783.
Le´pinoux-Chambaud, C and Eyer, J. (2013) Review on intermediate filaments of the nervous system and their pathological alterations Histochem Cell Biol 140:13–22.
Chung, B-M, et al (2013) Networking galore: intermediate filaments and cell migration. Curr Op Cell Biol 25: 600-612.
The Nuclear Lamins Primary Papers:
Shimi, T, et al (2011) The Role of Nuclear Lamin B1 in Cell Proliferation and Senescence. Genes and Development 25:2579-2593.
Shimi, T et al (2008) The A- and B- Type Nuclear Lamin Networks: Microdomains Involved in Chromatin Organization and Transcription. Genes and Development 22: 3409-3421.
Goldman, RD, et al (2004) Accumulation of Mutant Lamin A Causes Progressive Changes in Nuclear Architecture in Hutchinson-Gilford Progeria Syndrome. PNAS 101: 8963-8968.
Spann, T et al (2002)Alteration of nuclear lamin organization inhibits RNA polymerase II–dependent transcription J Cell Biol 156:603-608.
The Nuclear Lamins Reviews:
Dechat, T, et al (2008) Nuclear lamins: major factors in the structural organization and function of the nucleus and chromatin. Genes and Development 22: 832-853
Butin-Israeli, V. et al (2012) Nuclear Lamin Functions and Disease. Trends in Genetics 28: 464-471.
Burke, B. and Stewart, CL (2013) The Nuclear Lamins: Felxibility in Function. Nat Rev Mol Cell Biol 14: 13-24.