THE HUMAN PROTEIN ATLAS BLOG
Image of the week - Intermediate filaments
Welcome back to HPA image of the week! This week we highlight another organelle brought to us by Mikaela Wiking aka HPA_Illuminator, the intermediate filaments!
The expression of intermediate filaments can be extremely dependent on cell type, for example the intermediate filament protein group keratins, discussed in a previous IOTW, are key components in hair, nails and skin. For example, fluorescent microscopy imaging of KRT13 (keratin 13) shows that it is only expressed in A-431 cells, skin cancer cells, and not in U-2 OS (bone cancer) or HeLa (cervical cancer). We can measure protein expression by evaluating how many times the section of DNA coding for a gene (KRT13 here) is transcribed (converted) into RNA which is in turn translated into proteins. The RNAseq data for KRT13, describing the abundance of RNA in that cell type confirms that A-431 cells express this protein while the others (U-2 OS, and HeLa) do not.
Figure 1 shows the intermediate filament protein vimentin (VIM) in U-251 MG brain cancer cells (glioblastoma astrocytoma).
Intermediate filaments connect the cell membrane to the nucleus and other organelles, and provide mechanical support, helping the cell withstand physical stress (Lowery J. et al. 2015). It has been reported that intermediate filaments bind to mitochondria, helping positioning them within the cell and also affecting their motility. Cells where the gene coding for the intermediate filament protein VIM had been deleted showed higher mitochondrial motility, compared to the wild-type cells with normal VIM expression (Nekrasova O.E. et al. 2011). Recent studies have shown that this mitochondrial motility is essential for proper cellular signaling, particularly in neurons (Schwarz T.L. 2013).
This link to mitochondrial motility may be one factor as to why VIM has been linked to several diseases in the central nervous system (CNS) and the brain. Astrocytes, the most common type of cell in your brain, belong to a group of cells denoted glial cells, which provide support and protection to neurons in the CNS (Molofsky AV. and Deneen B., 2015 ). The number of astrocytes in an area in the brain can be abnormally up-regulated (referred to as astrocyte reactivity) due to destruction of neurons, from e.g. CNS injury or infection. If VIM and glial fibrillary acidic protein (GFAP), the principal intermediate filament protein in astrocytes, are not expressed the CNS damage will be more severe and gliosis (healing) will be impaired (Hol E.M. & Pekny M. 2015).
In recent years, astrocytes have become an important target for therapeutic strategies targeting diseases affecting the CNS. For example, a candidate for amyotrophic lateral sclerosis (ALS, a neurodegenerative disease), was evaluated in clinical trials, but unfortunately did not show clinical efficacy in stage 3 (Cudkowicz M.E. 2014).
The overexpression of VIM also appears contribute to cancer invasiveness, while conversely low expression decreases the invasive capacity of certain cancers ( Leduc C. & Etienne-Manneville S. 2015). This mechanism, which is believed to increase cell migration by maturation of focal adhesions could be a possible target for therapeutics aiming to control cancer spreading and aggressiveness.
We'd like to again thank all of the members of the Human Protein Atlas and particularly the Subcellular atlas for generating these stainings. A special thanks to Mikaela Wiking (HPA_Illuminator, credit to MizhirStarsurge) for contributing this image of the week article!