Talk:Cytoskeleton - Intermediate Filaments
Published on 27 Jan 2014
Robert Goldman (Northwestern U/MBL) Part 2: Nuclear Lamins
Lecture Overview: 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.
Speaker Bio: 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 PhD 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.
The lamin protein family
Genome Biol. 2011;12(5):222. doi: 10.1186/gb-2011-12-5-222. Epub 2011 May 31.
Dittmer TA1, Misteli T.
The lamins are the major architectural proteins of the animal cell nucleus. Lamins line the inside of the nuclear membrane, where they provide a platform for the binding of proteins and chromatin and confer mechanical stability. They have been implicated in a wide range of nuclear functions, including higher-order genome organization, chromatin regulation, transcription, DNA replication and DNA repair. The lamins are members of the intermediate filament (IF) family of proteins, which constitute a major component of the cytoskeleton. Lamins are the only nuclear IFs and are the ancestral founders of the IF protein superfamily. Lamins polymerize into fibers forming a complex protein meshwork in vivo and, like all IF proteins, have a tripartite structure with two globular head and tail domains flanking a central α-helical rod domain, which supports the formation of higher-order polymers. Mutations in lamins cause a large number of diverse human diseases, collectively known as the laminopathies, underscoring their functional importance.
Fig 5 - Good figure of nuclear lamina structure/function. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3219962/figure/F5/
Yeast cells do not express lamins (Dittmer and Misteli, 2011 PMID 21639948) and do not migrate, but have rigid cell walls that physically protect their genomes.