New role for the nuclear proteins, Lamins and its implications for cancer drug discovery


16 Oct 2017

New role for the nuclear proteins, Lamins and its implications for cancer drug discovery

 

By Dr Kundan Sengupta, Intermediate Fellow

IISER Pune 

Our recently published study in Molecular Cell Biology suggests a new role for the nuclear protein, Lamin, which is responsible for maintaining the shape and function of the nucleus.

The nucleus houses our DNA and is the control centre of our cells. Inside the nucleus is a roundish entity - the nucleolus, which makes a cousin of DNA, ribosomal Ribonucleic Acid (rRNA), an essential part of molecular machines inside the cells, referred to as ribosomes. These ribosomes make proteins that we are all made up of, such as the keratin proteins in our hair and nails. Our research group is interested in understanding what controls the shape of the nucleolus, as changes in nucleolar shape or numbers typically increase rRNA levels. Normal cells have 2 or 3 nucleoli, while cancer cells may have even 10 or more. What maintains nucleolar numbers in normal cells and how is this control cleverly hijacked in cancer cells resulting in multiple nucleoli? Since cancer cells multiply in an uncontrolled manner, they need more protein for their survival and therefore extra nucleoli enable them to survive and multiply rampantly.

Lamins are proteins that maintain shape and impart strength to the nucleus. In our recently published report we asked the question- do Lamins also control shape and function of the nucleolus. Peering deep into cells using a super resolution microscope, revealed that Lamins in addition to their location at the border of the nucleus, are also located right near the boundary of the nucleolus. Using a molecular approach, we reduced the levels of one of the three Lamins to less than ~30% in cells and much to our surprise, the nucleolus collapsed into a single, large irregular blob! Interestingly, restoring Lamins to their normal levels, brought back the two round and discrete nucleoli. Further, lowering Lamins, tripled the levels of ribosomal RNA.

In summary, our study for the first time suggests that Lamins in addition to the nucleus, also control the shape and function of the nucleolus. It remains to be understood in the not so distant future, if restoring or correcting the levels and function of Lamins, would allow us to reverse and hopefully even partially undo the damage and large-scale destruction that cancer cells unleash on the human body.  

 

Lamin B2 modulates nucleolar morphology, dynamics and function. Sen Gupta A & Sengupta K. Molecular Cellular Biology. October 2017

Banner image credit: Dr Kundan Sengupta. Cells typically have two independent and discrete nucleoli (red), Lamin protein (green) at the edge of the nucleus (blue).